Scholars@Duke
James R. Bain

James R. Bain

Professor in Medicine
Medicine, Endocrinology, Metabolism, and Nutrition
james.bain@duke.edu
Duke Box 104775, Durham, NC 27710
300 North Duke Street, Room 48-201, Duke Molecular Physiology Institute, Durham, NC 27701-2047

Selected Publications

Acute perioperative alterations in metabolism: A pilot study using mass spectrometry-based metabolomics.

Journal Article Surgery · December 30, 2024 OBJECTIVE: To characterize early physiologic stresses imposed by surgery by applying metabolomic analyses to deeply phenotype pre- and postoperative plasma and urine of patients undergoing elective surgical procedures. BACKGROUND: Patients experience perio ... Full text Link to item Cite

Type-2 Diabetes, Pancreatic Amylin, and Neuronal Metabolic Remodeling in Alzheimer's Disease.

Journal Article Mol Nutr Food Res · July 2024 Type-2 diabetes raises the risk for Alzheimer's disease (AD)-type dementia and the conversion from mild cognitive impairment to dementia, yet mechanisms connecting type-2 diabetes to AD remain largely unknown. Amylin, a pancreatic β-cell hormone co-secrete ... Full text Open Access Link to item Cite

Metabolomic and genetic architecture of gestational diabetes subtypes.

Journal Article Diabetologia · May 2024 AIMS/HYPOTHESIS: Physiological gestational diabetes mellitus (GDM) subtypes that may confer different risks for adverse pregnancy outcomes have been defined. The aim of this study was to characterise the metabolome and genetic architecture of GDM subtypes ... Full text Link to item Cite

Racial Differences in Vaginal Fluid Metabolites and Association with Systemic Inflammation Markers among Ovarian Cancer Patients: A Pilot Study.

Journal Article Cancers (Basel) · March 23, 2024 The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this ... Full text Link to item Cite

Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes.

Journal Article J Clin Endocrinol Metab · March 15, 2024 OBJECTIVES: Insulin resistance is associated with elevations in plasma branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids including tryptophan for uptake into β cells. To explore relationships between BCAAs and tryptophan metabolis ... Full text Link to item Cite

APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease.

Journal Article J Clin Invest · January 16, 2024 Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and ... Full text Open Access Link to item Cite

Metabolic factors associated with incident fracture among older adults with type 2 diabetes mellitus: a nested case-control study.

Journal Article Osteoporos Int · July 2023 UNLABELLED: Older adults with type 2 diabetes mellitus have an increased risk of fracture despite a paradoxically higher average bone mineral density. This study identified additional markers of fracture risk in this at-risk population. Non-esterified fatt ... Full text Open Access Link to item Cite

Maternal and Cord Blood Serum Metabolite Associations with Childhood Adiposity and Body Composition Outcomes.

Journal Article Metabolites · June 13, 2023 Maternal metabolites influence the size of newborns independently of maternal body mass index (BMI) and glycemia, highlighting the importance of maternal metabolism on offspring outcomes. This study examined associations of maternal metabolites during preg ... Full text Link to item Cite

Association of Maternal Metabolites and Metabolite Networks with Newborn Outcomes in a Multi-Ancestry Cohort.

Journal Article Metabolites · March 31, 2023 The in utero environment is important for newborn size at birth, which is associated with childhood adiposity. We examined associations between maternal metabolite levels and newborn birthweight, sum of skinfolds (SSF), and cord C-peptide in a multinationa ... Full text Link to item Cite

Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity.

Journal Article Endocrinol Diabetes Metab · January 2023 OBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the level ... Full text Link to item Cite

Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.

Journal Article J Alzheimers Dis · 2023 BACKGROUND: The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD). OBJECTI ... Full text Open Access Link to item Cite

Disrupted Circadian Rhythm of Epinephrine in Males With Youth-Onset Type 2 Diabetes.

Journal Article J Endocr Soc · December 15, 2022 CONTEXT: Blood pressure and plasma catecholamines normally decline during sleep and rapidly increase in early morning. This is blunted in adults with type 2 diabetes (T2D). OBJECTIVE: We hypothesize that increased sympatho-adrenal activity during sleep dif ... Full text Link to item Cite

Ecological memory of prior nutrient exposure in the human gut microbiome.

Journal Article ISME J · November 2022 Many ecosystems have been shown to retain a memory of past conditions, which in turn affects how they respond to future stimuli. In microbial ecosystems, community disturbance has been associated with lasting impacts on microbiome structure. However, wheth ... Full text Open Access Link to item Cite

A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.

Journal Article Ann Surg · June 1, 2022 OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the system ... Full text Link to item Cite

Path-level interpretation of Gaussian graphical models using the pair-path subscore.

Journal Article BMC Bioinformatics · January 5, 2022 BACKGROUND : Construction of networks from cross-sectional biological data is increasingly common. Many recent methods have been based on Gaussian graphical modeling, and prioritize estimation of conditional pairwise dependencies among nodes in the network ... Full text Link to item Cite

Evaluating immune response and metabolic related biomarkers pre-allogenic hematopoietic stem cell transplant in acute myeloid leukemia.

Journal Article PLoS One · 2022 Although hematopoietic stem cell transplantation (HCT) is the only curative treatment for acute myeloid leukemia (AML), it is associated with significant treatment related morbidity and mortality. There is great need for predictive biomarkers associated wi ... Full text Link to item Cite

Comparing the Chemical Profiles of Plant-Based and Traditional Meats Using GC–MS-Based Metabolomics

Journal Article LC-GC North America · January 1, 2022 As the consumer interest and market for plant-based meat alternatives grows, understanding the nutritional differences between alternative and traditional meats is essential. This article describes an untargeted gas chromatography–mass spectrometry (GC–MS) ... Full text Cite

Urine tricarboxylic acid cycle signatures of early-stage diabetic kidney disease.

Journal Article Metabolomics · December 20, 2021 INTRODUCTION: Urine tricarboxylic acid (TCA) cycle organic anions (OAs) are elevated in diabetes and may be biomarkers for diabetic kidney disease (DKD) progression. OBJECTIVES: We assessed associations of 10 urine TCA cycle OAs with estimated glomerular f ... Full text Open Access Link to item Cite

Maternal Metabolites Associated With Gestational Diabetes Mellitus and a Postpartum Disorder of Glucose Metabolism.

Journal Article J Clin Endocrinol Metab · October 21, 2021 CONTEXT: Gestational diabetes is associated with a long-term risk of developing a disorder of glucose metabolism. However, neither the metabolic changes characteristic of gestational diabetes in a large, multi-ancestry cohort nor the ability of metabolic c ... Full text Link to item Cite

Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street.

Journal Article Mol Metab · October 2021 BACKGROUND: A strong association of obesity and insulin resistance with increased circulating levels of branched-chain and aromatic amino acids and decreased glycine levels has been recognized in human subjects for decades. SCOPE OF REVIEW: More recently, ... Full text Link to item Cite

Circulating long chain acylcarnitines and outcomes in diabetic heart failure: an HF-ACTION clinical trial substudy.

Journal Article Cardiovasc Diabetol · August 3, 2021 BACKGROUND: Whether differences in circulating long chain acylcarnitines (LCAC) are seen in heart failure (HF) patients with and without diabetes mellitus (DM), and whether these biomarkers report on exercise capacity and clinical outcomes, remains unknown ... Full text Link to item Cite

A metabolomics comparison of plant-based meat and grass-fed meat indicates large nutritional differences despite comparable Nutrition Facts panels.

Journal Article Sci Rep · July 5, 2021 A new generation of plant-based meat alternatives-formulated to mimic the taste and nutritional composition of red meat-have attracted considerable consumer interest, research attention, and media coverage. This has raised questions of whether plant-based ... Full text Open Access Link to item Cite

Impact of lifestyle Intervention on branched-chain amino acid catabolism and insulin sensitivity in adolescents with obesity.

Journal Article Endocrinol Diabetes Metab · July 2021 UNLABELLED: Insulin resistance in adolescents with obesity associates with a sex-dependent metabolic 'signature' comprising branched-chain amino acids (BCAAs), glutamate and C3/C5 acylcarnitines (C3/C5), implicating altered flux through BCAA catabolic path ... Full text Link to item Cite

Effect of Bicarbonate on Net Acid Excretion, Blood Pressure, and Metabolism in Patients With and Without CKD: The Acid Base Compensation in CKD Study.

Journal Article Am J Kidney Dis · July 2021 RATIONALE & OBJECTIVE: Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participant ... Full text Link to item Cite

781-P: Beyond Glucosuria: Urine Metabolome Signature Associated with Dapagliflozin in Wild-Type Mice

Conference Diabetes · June 1, 2021 Background: Glucosuria is a hallmark feature of diabetes. When blood glucose exceeds 200 mg/dl, the amounts reaching the renal tubule overwhelm the capacity of glucose transport and cause glucosuria. SGLT2 inhibitors (SGLT2i) prevent reclamation of ... Full text Cite

Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study.

Journal Article Nutrients · May 22, 2021 We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one w ... Full text Link to item Cite

Parallel Multi-Omics in High-Risk Subjects for the Identification of Integrated Biomarker Signatures of Type 1 Diabetes.

Journal Article Biomolecules · March 4, 2021 BACKGROUND: Biomarkers are crucial for detecting early type-1 diabetes (T1D) and preventing significant β-cell loss before the onset of clinical symptoms. Here, we present proof-of-concept studies to demonstrate the potential for identifying integrated bio ... Full text Link to item Cite

A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism.

Journal Article J Biol Chem · 2021 Caloric restriction (CR) improves health span and life span of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging-associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is ... Full text Link to item Cite

A phase 2 trial of the somatostatin analog pasireotide to prevent GI toxicity and acute GVHD in allogeneic hematopoietic stem cell transplant.

Journal Article PLoS One · 2021 BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant ... Full text Link to item Cite

Novel plasma biomarkers improve discrimination of metabolic health independent of weight.

Journal Article Sci Rep · December 7, 2020 We sought to determine if novel plasma biomarkers improve traditionally defined metabolic health (MH) in predicting risk of cardiovascular disease (CVD) events irrespective of weight. Poor MH was defined in CATHGEN biorepository participants (n > 9300), a ... Full text Link to item Cite

A cell-nonautonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism.

Journal Article J Biol Chem · December 2, 2020 Caloric restriction (CR) improves health span and life span of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging-associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is ... Full text Link to item Cite

Muscle-Liver Trafficking of BCAA-Derived Nitrogen Underlies Obesity-Related Glycine Depletion.

Journal Article Cell Rep · November 10, 2020 Glycine levels are inversely associated with branched-chain amino acids (BCAAs) and cardiometabolic disease phenotypes, but biochemical mechanisms that explain these relationships remain uncharted. Metabolites and genes related to BCAA metabolism and nitro ... Full text Link to item Cite

Biomarkers Associated with Physical Resilience After Hip Fracture.

Journal Article J Gerontol A Biol Sci Med Sci · September 25, 2020 BACKGROUND: Clinically similar older adults demonstrate variable responses to health stressors, heterogeneity attributable to differences in physical resilience. However, molecular mechanisms underlying physical resilience are unknown. We previously derive ... Full text Link to item Cite

Metabolomic and genetic associations with insulin resistance in pregnancy.

Journal Article Diabetologia · September 2020 AIMS/HYPOTHESIS: Our study aimed to integrate maternal metabolic and genetic data related to insulin sensitivity during pregnancy to provide novel insights into mechanisms underlying pregnancy-induced insulin resistance. METHODS: Fasting and 1 h serum samp ... Full text Link to item Cite

526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease

Conference Diabetes · June 1, 2020 Background: Urine tricarboxylic acid (TCA) cycle organic anions (OAs) are elevated in diabetes and may be biomarkers for diabetic kidney disease (DKD) progression.Methods: We conducted an ancillary study to the Simu ... Full text Cite

Non-targeted urinary metabolomics in pregnancy and associations with fetal growth restriction.

Journal Article Sci Rep · March 24, 2020 Our objective was to identify metabolites associated with fetal growth restriction (FGR) by examining early and late pregnancy differences in non-targeted urinary metabolites among FGR cases and non-FGR controls. An exploratory case-control study within LI ... Full text Link to item Cite

Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries.

Journal Article J Clin Endocrinol Metab · October 1, 2019 CONTEXT: Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance. OBJECTIVE: To determine the association of cord blood metab ... Full text Link to item Cite

Assessing Vascular Markers of Diabetic Disease Progression Through Contrast Enhanced Ultrasound

Conference IEEE International Ultrasonics Symposium, IUS · October 1, 2019 Diabetic disease progression, resulting in diabetic kidney disease (DKD) increases the risk of kidney failure and is a strong predictor for patient mortality. Early detection of DKD could mitigate risks associated with DKD progression, but currently there ... Full text Cite

Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes.

Journal Article Metabolites · September 29, 2019 (1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin ... Full text Link to item Cite

Identification of Metabolic Changes in Ileum, Jejunum, Skeletal Muscle, Liver, and Lung in a Continuous I.V. Pseudomonas aeruginosa Model of Sepsis Using Nontargeted Metabolomics Analysis.

Journal Article Am J Pathol · September 2019 Sepsis is a multiorgan disease affecting the ileum and jejunum (small intestine), liver, skeletal muscle, and lung clinically. The specific metabolic changes in the ileum, jejunum, liver, skeletal muscle, and lung have not previously been investigated. Liv ... Full text Link to item Cite

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure.

Journal Article Sci Rep · June 3, 2019 Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants wit ... Full text Link to item Cite

Maternal metabolites during pregnancy are associated with newborn outcomes and hyperinsulinaemia across ancestries.

Journal Article Diabetologia · March 2019 AIMS/HYPOTHESIS: We aimed to determine the association of maternal metabolites with newborn adiposity and hyperinsulinaemia in a multi-ethnic cohort of mother-newborn dyads. METHODS: Targeted and non-targeted metabolomics assays were performed on fasting a ... Full text Link to item Cite

Age-Related Adverse Inflammatory and Metabolic Changes Begin Early in Adulthood.

Journal Article J Gerontol A Biol Sci Med Sci · February 15, 2019 Aging is characterized by deleterious immune and metabolic changes, but the onset of these changes is unknown. We measured immune and metabolic biomarkers in adults beginning at age 30. To our knowledge, this is the first study to evaluate these biomarkers ... Full text Open Access Link to item Cite

112: Urinary metabolomic profiles in pregnancy and association with fetal growth restriction

Conference American Journal of Obstetrics and Gynecology · January 2019 Full text Cite

Adverse Effects of Fenofibrate in Mice Deficient in the Protein Quality Control Regulator, CHIP.

Journal Article J Cardiovasc Dev Dis · August 15, 2018 We previously reported how the loss of CHIP expression (Carboxyl terminus of Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac dysfunction, which was accompanied by a failure to maintain ATP levels in the face of increased ener ... Full text Link to item Cite

Metabolic Changes with Base-Loading in CKD.

Journal Article Clin J Am Soc Nephrol · August 7, 2018 Full text Open Access Link to item Cite

Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid.

Journal Article Surg Obes Relat Dis · August 2018 BACKGROUND: Gastric bypass surgery for weight reduction often corrects dysglycemia in diabetic patients, but a full understanding of the underlying biochemical pathways continues to be investigated. OBJECTIVES: To explore the effects of weight loss by surg ... Full text Link to item Cite

Combined Inflammation and Metabolism Biomarker Indices of Robust and Impaired Physical Function in Older Adults.

Journal Article J Am Geriatr Soc · July 2018 OBJECTIVES: To determine whether combinations of inflammatory markers are related to physical function. DESIGN AND SUBJECTS: secondary analysis of baseline of three observational studies of community-dwelling older adults MEASUREMENTS: The baseline data fr ... Full text Open Access Link to item Cite

Dietary Patterns among Asian Indians Living in the United States Have Distinct Metabolomic Profiles That Are Associated with Cardiometabolic Risk.

Journal Article J Nutr · July 1, 2018 BACKGROUND: Recent studies, primarily in non-Hispanic whites, suggest that dietary patterns have distinct metabolomic signatures that may influence disease risk. However, evidence in South Asians, a group with unique dietary patterns and a high prevalence ... Full text Open Access Link to item Cite

Physiological mechanisms of sustained fumagillin-induced weight loss.

Journal Article JCI Insight · March 8, 2018 Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feedi ... Full text Link to item Cite

Untargeted metabolomics analysis of ischemia-reperfusion-injured hearts ex vivo from sedentary and exercise-trained rats.

Journal Article Metabolomics · January 2018 INTRODUCTION: The effects of exercise on the heart and its resistance to disease are well-documented. Recent studies have identified that exercise-induced resistance to arrhythmia is due to the preservation of mitochondrial membrane potential. OBJECTIVES: ... Full text Link to item Cite

A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor.

Journal Article Front Oncol · 2018 Olfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer but its function is not well understood. Through in silico and in vitro analyses, we identified 24 agonists and 1 antagonist for this re ... Full text Open Access Link to item Cite

Effects of the kinase inhibitor sorafenib on heart, muscle, liver and plasma metabolism in vivo using non-targeted metabolomics analysis.

Journal Article Br J Pharmacol · December 2017 BACKGROUND AND PURPOSE: The human kinome consists of roughly 500 kinases, including 150 that have been proposed as therapeutic targets. Protein kinases regulate an array of signalling pathways that control metabolism, cell cycle progression, cell death, di ... Full text Link to item Cite

Recommendations for Improving Identification and Quantification in Non-Targeted, GC-MS-Based Metabolomic Profiling of Human Plasma.

Journal Article Metabolites · August 25, 2017 The field of metabolomics as applied to human disease and health is rapidly expanding. In recent efforts of metabolomics research, greater emphasis has been placed on quality control and method validation. In this study, we report an experience with qualit ... Full text Link to item Cite

Exercise-Induced Alterations in Skeletal Muscle, Heart, Liver, and Serum Metabolome Identified by Non-Targeted Metabolomics Analysis.

Journal Article Metabolites · August 8, 2017 BACKGROUND: The metabolic and physiologic responses to exercise are increasingly interesting, given that regular physical activity enhances antioxidant capacity, improves cardiac function, and protects against type 2 diabetes. The metabolic interactions be ... Full text Link to item Cite

Sildenafil Treatment in Heart Failure With Preserved Ejection Fraction: Targeted Metabolomic Profiling in the RELAX Trial.

Journal Article JAMA Cardiol · August 1, 2017 IMPORTANCE: Phosphodiesterase-5 inhibition with sildenafil compared with a placebo had no effect on the exercise capacity or clinical status of patients with heart failure with preserved ejection fraction (HFpEF) in the PhosphodiesteRasE-5 Inhibition to Im ... Full text Link to item Cite

Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo.

Journal Article Metabolites · July 29, 2017 BACKGROUND: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype i ... Full text Link to item Cite

Targeted Metabolomics Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose, and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups.

Journal Article Diabetes Care · July 2017 OBJECTIVE: We used targeted metabolomics in pregnant mothers to compare maternal metabolite associations with maternal BMI, glycemia, and insulin sensitivity. RESEARCH DESIGN AND METHODS: Targeted metabolomic assays of clinical metabolites, amino acids, an ... Full text Link to item Cite

Maternal BMI and Glycemia Impact the Fetal Metabolome.

Journal Article Diabetes Care · July 2017 OBJECTIVE: We used targeted metabolomics to determine associations of maternal BMI and glucose levels with cord blood metabolites and associations of cord blood metabolites with newborn birth weight and adiposity in mother-offspring dyads. RESEARCH DESIGN ... Full text Link to item Cite

Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo.

Journal Article Metabolites · June 22, 2017 Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase depend ... Full text Link to item Cite

Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes.

Journal Article Diabetologia · March 2017 AIMS/HYPOTHESIS: Maternal obesity increases the risk for large-for-gestational-age birth and excess newborn adiposity, which are associated with adverse long-term metabolic outcomes in offspring, probably due to effects mediated through the intrauterine en ... Full text Link to item Cite

Mixture model normalization for non-targeted gas chromatography/mass spectrometry metabolomics data.

Journal Article BMC Bioinformatics · February 2, 2017 BACKGROUND: Metabolomics offers a unique integrative perspective for health research, reflecting genetic and environmental contributions to disease-related phenotypes. Identifying robust associations in population-based or large-scale clinical studies dema ... Full text Link to item Cite

Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations.

Journal Article J Gerontol A Biol Sci Med Sci · November 2016 BACKGROUND: Older age and obesity are associated with metabolic dysregulation; the mechanism by which these factors impact metabolism across the lifespan is important, but relatively unknown. We evaluated a panel of amino acids (AAs) and acylcarnitines (AC ... Full text Link to item Cite

Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis.

Journal Article Int J Biochem Cell Biol · October 2016 Studies of skeletal muscle disuse, either in patients on bed rest or experimentally in animals (immobilization), have demonstrated that decreased protein synthesis is common, with transient parallel increases in protein degradation. Muscle disuse atrophy i ... Full text Link to item Cite

Cardiomyocyte-Specific Human Bcl2-Associated Anthanogene 3 P209L Expression Induces Mitochondrial Fragmentation, Bcl2-Associated Anthanogene 3 Haploinsufficiency, and Activates p38 Signaling.

Journal Article Am J Pathol · August 2016 The Bcl2-associated anthanogene (BAG) 3 protein is a member of the BAG family of cochaperones, which supports multiple critical cellular processes, including critical structural roles supporting desmin and interactions with heat shock proteins and ubiquiti ... Full text Link to item Cite

Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism.

Journal Article Metabolomics · August 2016 INTRODUCTION: Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more clinically significant in older persons. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung inju ... Full text Link to item Cite

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure.

Journal Article J Am Heart Assoc · July 29, 2016 BACKGROUND: Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine ... Full text Open Access Link to item Cite

Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export.

Journal Article Mol Metab · July 2016 OBJECTIVE: A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obes ... Full text Link to item Cite

Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth.

Journal Article Diabetes · July 2016 Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry ... Full text Link to item Cite

Proteomic Profiling Reveals Adaptive Responses to Surgical Myocardial Ischemia-Reperfusion in Hibernating Arctic Ground Squirrels Compared to Rats.

Journal Article Anesthesiology · June 2016 BACKGROUND: Hibernation is an adaptation to extreme environments known to provide organ protection against ischemia-reperfusion (I/R) injury. An unbiased systems approach was utilized to investigate hibernation-induced changes that are characteristic of th ... Full text Link to item Cite

Research Resource: Roles for Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) in Systems Metabolism.

Journal Article Mol Endocrinol · May 2016 A number of epidemiological studies have implicated calcium (Ca(2+)) signaling as a major factor in obesity that contributes to aberrant systems metabolism. Somewhat paradoxically, obesity correlates with decreased circulating Ca(2+) levels, leading to inc ... Full text Link to item Cite

Human amylin proteotoxicity impairs protein biosynthesis, and alters major cellular signaling pathways in the heart, brain and liver of humanized diabetic rat model in vivo.

Journal Article Metabolomics · May 2016 INTRODUCTION: Chronic hypersecretion of the 37 amino acid amylin is common in type 2 diabetics (T2D). Recent studies implicate human amylin aggregates cause proteotoxicity (cell death induced by misfolded proteins) in both the brain and the heart. OBJECTIV ... Full text Link to item Cite

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Journal Article Cell · February 25, 2016 Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed t ... Full text Link to item Cite

Metabolic profiling in Prader-Willi syndrome and nonsyndromic obesity: sex differences and the role of growth hormone.

Journal Article Clin Endocrinol (Oxf) · December 2015 OBJECTIVES: To identify metabolic factors controlling appetite and insulin sensitivity in PWS and assess effects of GH treatment. METHODS: We compared amino acids, fatty acids and acylcarnitines in GH-treated and untreated PWS children and obese and lean c ... Full text Open Access Link to item Cite

Metabolomic Quantitative Trait Loci (mQTL) Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis.

Journal Article PLoS Genet · November 2015 Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA), long-chain dicarboxylacylcarnitine (LCDA) and medium chain acylcarnitine (MCA) metabolites are heritable and predict cardiovascular disease (CVD) events. Little is known about the bi ... Full text Open Access Link to item Cite

Non-targeted metabolomics of Brg1/Brm double-mutant cardiomyocytes reveals a novel role for SWI/SNF complexes in metabolic homeostasis.

Journal Article Metabolomics · October 1, 2015 Mammalian SWI/SNF chromatin-remodeling complexes utilize either BRG1 or Brm as alternative catalytic subunits to alter the position of nucleosomes and regulate gene expression. Genetic studies have demonstrated that SWI/SNF complexes are required during ca ... Full text Link to item Cite

Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans.

Journal Article Diabetologia · October 2015 AIMS/HYPOTHESES: Obesity is associated with decreased insulin sensitivity (IS) and elevated plasma branched-chain amino acids (BCAAs). The purpose of this study was to investigate the relationship between BCAA metabolism and IS in overweight (OW) individua ... Full text Link to item Cite

MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet.

Journal Article Cardiovasc Diabetol · August 5, 2015 BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced a ... Full text Link to item Cite

Muscle ring finger-3 protects against diabetic cardiomyopathy induced by a high fat diet.

Journal Article BMC Endocr Disord · July 28, 2015 BACKGROUND: The pathogenesis of diabetic cardiomyopathy (DCM) involves the enhanced activation of peroxisome proliferator activating receptor (PPAR) transcription factors, including the most prominent isoform in the heart, PPARα. In cancer cells and adipoc ... Full text Link to item Cite

Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes.

Journal Article Metabolomics · April 2015 The muscle-specific ubiquitin ligases MuRF1, MuRF2, MuRF3 have been reported to have overlapping substrate specificities, interacting with each other as well as proteins involved in metabolism and cardiac function. In the heart, all three MuRF family prote ... Full text Link to item Cite

Effect of aerobic training on the host systemic milieu in patients with solid tumours: an exploratory correlative study.

Journal Article Br J Cancer · March 3, 2015 BACKGROUND: Few studies have investigated the effects of exercise on modulation of host factors in cancer patients. We investigated the efficacy of chronic aerobic training on multiple host-related effector pathways in patients with solid tumours. PATIENTS ... Full text Link to item Cite

Effect of aerobic training on the host systemic milieu in patients with solid tumours: An exploratory correlative study

Journal Article British Journal of Cancer · March 3, 2015 Background: Few studies have investigated the effects of exercise on modulation of host factors in cancer patients. We investigated the efficacy of chronic aerobic training on multiple host-related effector pathways in patients with solid tumours.Patients ... Full text Cite

Sex differences in biomarkers associated with insulin resistance in obese adolescents: metabolomic profiling and principal components analysis.

Journal Article J Clin Endocrinol Metab · December 2014 OBJECTIVE: Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as bi ... Full text Link to item Cite

Metabomxtr: an R package for mixture-model analysis of non-targeted metabolomics data.

Journal Article Bioinformatics · November 15, 2014 SUMMARY: Non-targeted metabolomics technologies often yield data in which abundance for any given metabolite is observed and quantified for some samples and reported as missing for other samples. Apparent missingness can be due to true absence of the metab ... Full text Link to item Cite

A transcription factor links growth rate and metabolism in the hypersaline adapted archaeon Halobacterium salinarum.

Journal Article Mol Microbiol · September 2014 Co-ordinating metabolism and growth is a key challenge for all organisms. Despite fluctuating environments, cells must produce the same metabolic outputs to thrive. The mechanisms underlying this 'growth homeostasis' are known in bacteria and eukaryotes, b ... Full text Link to item Cite

Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice.

Journal Article J Lipid Res · July 2014 Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. The high-fat lard diet induces obesity and fatty liver in C57BL/6J mice and suppresses expression of the PPAR-target gene, FA elongase 5 (Elovl5 ... Full text Link to item Cite

Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.

Journal Article J Clin Endocrinol Metab · June 2014 OBJECTIVE: Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. METHODS: We used targ ... Full text Link to item Cite

Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans.

Journal Article Am J Clin Nutr · March 2014 BACKGROUND: Epidemiologic evidence has suggested that diets with a high ratio of palmitic acid (PA) to oleic acid (OA) increase risk of cardiovascular disease (CVD). OBJECTIVE: To gain additional insights into the relative effect of dietary fatty acids and ... Full text Link to item Cite

Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization.

Journal Article Atherosclerosis · January 2014 OBJECTIVE: To validate independent associations between branched-chain amino acids (BCAA) and other metabolites with coronary artery disease (CAD). METHODS: We conducted mass-spectrometry-based profiling of 63 metabolites in fasting plasma from 1983 sequen ... Full text Link to item Cite

Effects of HIV infection on the metabolic and hormonal status of children with severe acute malnutrition.

Journal Article PLoS One · 2014 BACKGROUND: HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood. METHODS: We conducted a prospective cohort study of 75 sev ... Full text Link to item Cite

Metabolomics reveals broad-scale metabolic perturbations in hyperglycemic mothers during pregnancy.

Journal Article Diabetes Care · 2014 OBJECTIVE To characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG). RESEARCH DESIGN AND METHODS We compared fasting serum from an oral glucose tolerance tes ... Full text Link to item Cite

Race and sex differences in small-molecule metabolites and metabolic hormones in overweight and obese adults.

Journal Article OMICS · December 2013 In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this ... Full text Link to item Cite

Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation.

Journal Article Diabetes · October 2013 Sirt3 is an NAD(+)-dependent deacetylase that regulates mitochondrial function by targeting metabolic enzymes and proteins. In fasting mice, Sirt3 expression is decreased in skeletal muscle resulting in increased mitochondrial protein acetylation. Deletion ... Full text Link to item Cite

Gut microbiota from twins discordant for obesity modulate metabolism in mice.

Journal Article Science · September 6, 2013 The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels o ... Full text Link to item Cite

Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness.

Journal Article Metabolism · July 2013 OBJECTIVE: To identify novel biomarkers through metabolomic profiles that distinguish metabolically well (MW) from metabolically unwell (MUW) individuals, independent of body mass index (BMI). MATERIALS/METHODS: This study was conducted as part of the Meas ... Full text Link to item Cite

A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults.

Journal Article Diabetes · April 2013 Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens co ... Full text Link to item Cite

Pathogenesis of A⁻β⁺ ketosis-prone diabetes.

Journal Article Diabetes · March 2013 A⁻β⁺ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible β-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. ... Full text Link to item Cite

Research resource: tissue- and pathway-specific metabolomic profiles of the steroid receptor coactivator (SRC) family.

Journal Article Mol Endocrinol · February 2013 The rapidly growing family of transcriptional coregulators includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have emerged as important regulators of metabolic homeostasis, inc ... Full text Link to item Cite

Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization.

Journal Article J Lipid Res · December 2012 Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. Identifying novel regulators of mitochondrial bioenergetics will broaden our understanding of regulatory checkpoints that coordinate complex metabolic pathways. We previo ... Full text Link to item Cite

Marginal vitamin B-6 deficiency decreases plasma (n-3) and (n-6) PUFA concentrations in healthy men and women.

Journal Article J Nutr · October 2012 Previous animal studies showed that severe vitamin B-6 deficiency altered fatty acid profiles of tissue lipids, often with an increase of linoleic acid and a decrease of arachidonic acid. However, little is known about the extent to which vitamin B-6 defic ... Full text Link to item Cite

Analysis of serum metabolic profiles in women with endometrial cancer and controls in a population-based case-control study.

Journal Article J Clin Endocrinol Metab · September 2012 CONTEXT: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk asse ... Full text Link to item Cite

Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.

Journal Article Diabetes · September 2012 A peptide designed to induce apoptosis of endothelium in white adipose tissue (WAT) decreases adiposity. The goal of this work is to determine whether targeting of WAT endothelium results in impaired glucose regulation as a result of impaired WAT function. ... Full text Link to item Cite

Daily Variation of Serum Acylcarnitines and Amino Acids.

Journal Article Metabolomics · August 2012 To characterize daily variation of amino acids (AAs) and acylcarnitines (ACs) in response to feeding and activity, we measured serum metabolites at various times and after various activities during the day. Subjects were admitted overnight for serial serum ... Full text Link to item Cite

Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease.

Journal Article Am Heart J · May 2012 BACKGROUND: Cardiovascular risk models remain incomplete. Small-molecule metabolites may reflect underlying disease and, as such, serve as novel biomarkers of cardiovascular risk. METHODS: We studied 2,023 consecutive patients undergoing cardiac catheteriz ... Full text Link to item Cite

Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss.

Journal Article Diabetologia · February 2012 AIMS/HYPOTHESIS: Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. METHODS: Targeted mass spectrometry-base ... Full text Link to item Cite

Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

Journal Article PLoS One · 2012 OBJECTIVES: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to dete ... Full text Open Access Link to item Cite

Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis.

Journal Article PLoS One · 2012 The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, s ... Full text Link to item Cite

Effect of heparin administration on metabolomic profiles in samples obtained during cardiac catheterization.

Journal Article Circ Cardiovasc Genet · December 2011 BACKGROUND: Metabolic profiling holds promise for early detection of coronary artery disease and assessing risk for ischemic events. Heparin is frequently administered (1) to treat acute coronary syndromes; and (2) during routine cardiac catheterization pr ... Full text Link to item Cite

The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins.

Journal Article Sci Transl Med · October 26, 2011 Understanding how the human gut microbiota and host are affected by probiotic bacterial strains requires carefully controlled studies in humans and in mouse models of the gut ecosystem where potentially confounding variables that are difficult to control i ... Full text Link to item Cite

Plasma acylcarnitines are associated with physical performance in elderly men.

Journal Article J Gerontol A Biol Sci Med Sci · May 2011 BACKGROUND: Metabolic profiling might provide insight into the biologic underpinnings of disability in older adults. METHODS: A targeted mass spectrometry-based platform was used to identify and quantify 45 plasma acylcarnitines in 77 older men with a mean ... Full text Link to item Cite

Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.

Journal Article Sci Transl Med · April 27, 2011 Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better m ... Full text Link to item Cite

Abstract LB-454: Serum metabolic profiles and endometrial cancer

Journal Article Cancer Research · April 15, 2011 AbstractObesity is a risk factor for endometrial cancer yet the molecular mechanism underlying this relationship is not fully understood. Obesity is associated with major metabolic changes; however, the rela ... Full text Cite

Effect of caloric restriction with and without exercise on metabolic intermediates in nonobese men and women.

Journal Article J Clin Endocrinol Metab · February 2011 OBJECTIVES: The objective of the study was to evaluate whether serum concentrations of metabolic intermediates are related to adiposity and insulin sensitivity (Si) in overweight healthy subjects and compare changes in metabolic intermediates with similar ... Full text Link to item Cite

Exercise-induced changes in metabolic intermediates, hormones, and inflammatory markers associated with improvements in insulin sensitivity.

Journal Article Diabetes Care · January 2011 OBJECTIVE: To understand relationships between exercise training-mediated improvements in insulin sensitivity (S(I)) and changes in circulating concentrations of metabolic intermediates, hormones, and inflammatory mediators. RESEARCH DESIGN AND METHODS: Ta ... Full text Open Access Link to item Cite

The coactivator SRC-1 is an essential coordinator of hepatic glucose production.

Journal Article Cell Metab · December 1, 2010 Gluconeogenesis makes a major contribution to hepatic glucose production, a process critical for survival in mammals. In this study, we identify the p160 family member, SRC-1, as a key coordinator of the hepatic gluconeogenic program in vivo. SRC-1-null mi ... Full text Link to item Cite

Comprehensive Metabolic Analysis for Understanding of Disease

Journal Article · December 1, 2010 Comprehensive measurement of intermediary metabolites and changes in metabolic activity lead to the improved detection and understanding of diseases. Metabolomics is increasingly getting integrated with genomic and transcriptomic profiling methods. This ch ... Full text Cite

Dissecting the in vivo metabolic potential of two human gut acetogens.

Journal Article J Biol Chem · July 16, 2010 Fermenting microbial communities generate hydrogen; its removal through the production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for ... Full text Link to item Cite

Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.

Journal Article Circ Cardiovasc Genet · April 2010 BACKGROUND: Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events. METHODS AND RESULTS: We performed mass-spectrometry-based profil ... Full text Open Access Link to item Cite

Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men.

Journal Article Diabetologia · April 2010 AIMS/HYPOTHESIS: Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. ME ... Full text Link to item Cite

Leptin therapy in insulin-deficient type I diabetes.

Journal Article Proc Natl Acad Sci U S A · March 16, 2010 In nonobese diabetic mice with uncontrolled type 1 diabetes, leptin therapy alone or combined with low-dose insulin reverses the catabolic state through suppression of hyperglucagonemia. Additionally, it mimics the anabolic actions of insulin monotherapy a ... Full text Link to item Cite

SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation.

Journal Article Nature · March 4, 2010 Sirtuins are NAD(+)-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation ... Full text Link to item Cite

Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women.

Journal Article Diabetes Care · September 2009 OBJECTIVE: To determine whether circulating metabolic intermediates are related to insulin resistance and beta-cell dysfunction in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: In 73 sedentary, overweight to obese, dyslipidemic indi ... Full text Link to item Cite

Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion.

Journal Article Circulation · April 7, 2009 BACKGROUND: Human myocardial metabolism has been incompletely characterized in the setting of surgical cardioplegic arrest and ischemia/reperfusion. Furthermore, the effect of preexisting ventricular state on ischemia-induced metabolic derangements has not ... Full text Link to item Cite

A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.

Journal Article Cell Metab · April 2009 Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis ... Full text Link to item Cite

The STEDMAN project: biophysical, biochemical and metabolic effects of a behavioral weight loss intervention during weight loss, maintenance, and regain.

Journal Article OMICS · February 2009 The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) Project uses comprehensive metabolic profiling to probe biochemical mechanisms of weight loss in humans. Measurements at baseline, 2 and 4 weeks, 6 and 12 months included diet, body com ... Full text Link to item Cite

High heritability of metabolomic profiles in families burdened with premature cardiovascular disease.

Journal Article Mol Syst Biol · 2009 Integration of genetic and metabolic profiling holds promise for providing insight into human disease. Coronary artery disease (CAD) is strongly heritable, but the heritability of metabolomic profiles has not been evaluated in humans. We performed quantita ... Full text Link to item Cite

Genetic networks of liver metabolism revealed by integration of metabolic and transcriptional profiling.

Journal Article PLoS Genet · March 14, 2008 Although numerous quantitative trait loci (QTL) influencing disease-related phenotypes have been detected through gene mapping and positional cloning, identification of the individual gene(s) and molecular pathways leading to those phenotypes is often elus ... Full text Link to item Cite

Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.

Journal Article Cell Metab · January 2008 Previous studies have suggested that insulin resistance develops secondary to diminished fat oxidation and resultant accumulation of cytosolic lipid molecules that impair insulin signaling. Contrary to this model, the present study used targeted metabolomi ... Full text Link to item Cite

Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle.

Journal Article Am J Physiol Endocrinol Metab · December 2007 Insulin resistance and type 2 diabetes are frequently accompanied by lipid accumulation in skeletal muscle. However, it is unknown whether primary lipid deposition in skeletal muscle is sufficient to cause insulin resistance or whether the type of muscle f ... Full text Link to item Cite

Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver.

Journal Article Cell Metab · July 2007 Hepatic steatosis, the accumulation of lipids in the liver, is widely believed to result in insulin resistance. To test the causal relationship between hepatic steatosis and insulin resistance, we generated mice that overexpress acyl-CoA:diacylglycerol acy ... Full text Link to item Cite

Chemical knockout of pantothenate kinase reveals the metabolic and genetic program responsible for hepatic coenzyme A homeostasis.

Journal Article Chem Biol · March 2007 Coenzyme A (CoA) is the major acyl group carrier in intermediary metabolism. Hopantenate (HoPan), a competitive inhibitor of the pantothenate kinases, was used to chemically antagonize CoA biosynthesis. HoPan dramatically reduced liver CoA and mice develop ... Full text Link to item Cite

TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism.

Journal Article Science · June 23, 2006 During fasting, increased concentrations of circulating catecholamines promote the mobilization of lipid stores from adipose tissue in part by phosphorylating and inactivating acetyl-coenzyme A carboxylase (ACC), the rate-limiting enzyme in fatty acid synt ... Full text Link to item Cite

The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: Rationale and design.

Journal Article Contemp Clin Trials · December 2005 This paper outlines the rationale and design of the Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project, in which detailed biologic profiling of three hundred and fifty obese individuals (body mass index (BMI): 30-50 kg/m ... Full text Link to item Cite

An adenovirus vector for efficient RNA interference-mediated suppression of target genes in insulinoma cells and pancreatic islets of langerhans.

Journal Article Diabetes · September 2004 Silencing gene expression by RNA interference (RNAi) can provide insight into gene function but requires efficient delivery of small interfering RNAs (siRNAs) into cells. Introduction of exogenous nucleic acids can be especially difficult in cultured pancr ... Full text Link to item Cite

Tissue-culture surfaces with mixtures of aminated and fluorinated functional groups. Part 2. Growth and function of transgenic rat insulinoma cells (betaG I/17).

Journal Article J Biomater Sci Polym Ed · 2003 Interactions of transplantable cells with synthetic polymers can influence the function of biohybrid artificial organs. This study explored growth and secretion of human insulin by betaG I/17 cells cultured on surfaces bearing diamine groups (N2), trifluor ... Full text Link to item Cite

Tissue-culture surfaces with mixtures of aminated and fluorinated functional groups. Part 1. Synthesis and characterization.

Journal Article J Biomater Sci Polym Ed · 2003 Surface chemistry of culture dishes can have profound effects on the phenotype of cultured cells. In the present study, chemisorption from aqueous, binary mixtures of organosilanes onto borosilicate glass created surfaces bearing diamine groups (N2), trifl ... Full text Link to item Cite

Glycophase glass revisited: protein adsorption and cell growth on glass surfaces bearing immobilized glycerol monosaccharides.

Journal Article Biomaterials · August 2002 Gamma-Glycerylpropylsilyl or "glycophase" glass has been promoted as a non-fouling surface, resistant to protein adsorption and cell attachment, on which one can immobilize oligopeptide ligands, and thus create cell-type-specific culture surfaces. The pres ... Full text Link to item Cite

RESPIRATORY AIDS

Journal Article · 2002 The present invention is directed to materials that assist respiration of living cells contained in cell-containing systems. The materials form air-filled conduits or channels through which gases, such as oxygen and carbon dioxide, can readily exchange by ... Cite

RESPIRATORY AIDS

Journal Article · 2000 The present invention is directed to materials that assist respiration of living cells contained in cell-containing systems. The materials form air-filled conduits or channels through which gases, such as oxygen and carbon dioxide, can readily exchange by ... Cite

Prosthesis for tensile load-carrying tissue and method of manufacture

Journal Article · 1993 The inventive article is a ligament or tendon prosthesis having multiple longitudinally parallel strands of microporous expanded polytetrafluoroethylene, the individual strands having an average porosity greater than 30% in the areas requiring tissue ingro ... Cite

Prosthesis for tensile-load-carrying tissue and method of manufacture

Journal Article · 1991 The inventive article is a ligament or tendon prosthesis having multiple longitudinally parallel strands of microporous expanded polytetrafluoroethylene, the individual strands having an average porosity greater than 30% in the areas requiring tissue ingro ... Cite

A method of making a synthetic prosthesis for replacing or repair of ligaments or tendons

Journal Article · 1986 A method for making a tensile load-bearing tissue prosthesis (10) comprises forming a plurality of elongate loops around at least two spaced-apart pins from a continuous filament of strand material, gathering the loop ends at one end of the loop to form an ... Cite

A synthetic prosthesis for replacement or repair of ligaments or tendons

Journal Article · 1984 The inventive article is a ligament or tendon prosthesis (10) having multiple longitudinally parallel strands (20) of microporous expanded polytetrafluoroethylene, the individual strands having an average porosity greater than 30% in the areas requiring ti ... Cite