Deborah Marie Muoio

Conference Circulation Research · August 2025 Cardiomyocytes (CMs) undergo metabolic and contractile reprogramming during cardiac stress and injury. This reprogramming response includes a fuel metabolic shift to a more fetal-like or immature state with downregulation in fatty acid ... Full text Cite

212-OR: Hepatic Overexpression of ACSS3 Alters Glucose Control and Fatty Acid Metabolism in Lean Mice

Conference Diabetes · June 20, 2025 Introduction and Objective: Short chain fatty acids (SCFAs) are associated with adverse metabolic outcomes; however, little is known about their link to metabolic disease. Emerging evidence suggests that in addition to acting as signaling molecules ... Full text Cite

Ketogenesis mitigates metabolic dysfunction-associated steatotic liver disease through mechanisms that extend beyond fat oxidation.

Journal Article J Clin Invest · June 16, 2025 The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH) involves alterations in both liver-autonomous and systemic metabolism that influence the liver's balance of fat a ... Full text Link to item Cite

Effect of in utero metformin exposure in gestational diabetes mellitus on infant mesenchymal stem cell metabolism.

Journal Article Am J Physiol Endocrinol Metab · April 1, 2025 Offspring exposed to metformin treatment for gestational diabetes mellitus (GDM) experience altered growth patterns that increase the risk for developing cardiometabolic diseases later in life. The adaptive cellular mechanisms underlying these patterns rem ... Full text Link to item Cite

The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research.

Journal Article Nat Metab · March 2025 The constant expansion of the field of metabolic research has led to more nuanced and sophisticated understanding of the complex mechanisms that underlie metabolic functions and diseases. Collaborations with scientists of various fields such as neuroscienc ... Full text Link to item Cite

Formation of I2+III2 supercomplex rescues respiratory chain defects.

Journal Article Cell Metab · February 4, 2025 Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversi ... Full text Link to item Cite

Ketogenesis protects against MASLD-MASH progression through mechanisms that extend beyond overall fat oxidation rate.

Journal Article bioRxiv · December 21, 2024 The progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) to metabolic-dysfunction-associated steatohepatitis (MASH) involves complex alterations in both liver-autonomous and systemic metabolism that influence the liver's balance ... Full text Link to item Cite

Direct mitochondrial import of lactate supports resilient carbohydrate oxidation.

Journal Article bioRxiv · October 8, 2024 Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate is an important energy source for many organs, but first must be oxidized to pyruvate for entry into the tricarboxylic acid cycle (TCA ... Full text Link to item Cite

Translating metabolic and cardiovascular research into effective treatments: What's next?

Journal Article Cell · July 25, 2024 The future of healthcare for cardiovascular diseases holds immense promise, not only based in new discoveries in cardiac metabolism but also in translating them to solutions for critical challenges faced by society. Here, ten scientists share their insight ... Full text Link to item Cite

Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding.

Journal Article Cell Metab · February 6, 2024 Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. No ... 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

Challenges and opportunities in targeting metabolism.

Journal Article Cell Chem Biol · September 21, 2023 Over the past decade or two, targeting metabolism has been effective in the treatment of many diseases and disorders, particularly cancer. In a metabolism focus issue in Cell Chemical Biology, this Voices piece asks researchers from a range of backgrounds: ... Full text Link to item Cite

Pyruvate-supported flux through medium-chain ketothiolase promotes mitochondrial lipid tolerance in cardiac and skeletal muscles.

Journal Article Cell Metab · June 6, 2023 Even-chain acylcarnitine (AC) metabolites, most of which are generated as byproducts of incomplete fatty acid oxidation (FAO), are viewed as biomarkers of mitochondrial lipid stress attributable to one or more metabolic bottlenecks in the β-oxidation pathw ... Full text Link to item Cite

Acetyl-CoA carboxylase 1 is a suppressor of the adipocyte thermogenic program.

Journal Article Cell Rep · May 30, 2023 Disruption of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) in mice induces browning in inguinal white adipose tissue (iWAT). However, adipocyte FASN knockout (KO) increases acetyl-coenzyme A (CoA) and malonyl-CoA in additio ... Full text Link to item Cite

RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure.

Journal Article J Clin Invest · May 1, 2023 During the development of heart failure (HF), the capacity for cardiomyocyte (CM) fatty acid oxidation (FAO) and ATP production is progressively diminished, contributing to pathologic cardiac hypertrophy and contractile dysfunction. Receptor-interacting pr ... Full text Link to item Cite

Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population.

Journal Article Clin J Am Soc Nephrol · February 1, 2023 BACKGROUND: Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanic/Latino people, a population with high risk for metabolic disease. ME ... Full text Link to item Cite

Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans.

Conference JCI Insight · January 10, 2023 BACKGROUNDAt the onset of exercise, the speed at which phosphocreatine (PCr) decreases toward a new steady state (PCr on-kinetics) reflects the readiness to activate mitochondrial ATP synthesis, which is secondary to Acetyl-CoA availability in skeletal mus ... Full text Link to item Cite

Abstract 2737: Stress-induced mitochondrial remodeling and metabolic resilience

Conference Journal of Biological Chemistry · 2023 Full text Cite

Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism.

Journal Article Mol Metab · December 2022 OBJECTIVE: SGLT2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes; the underlying mechanism may be metabolic adaptations due to urinary glucose loss. Here, we investigated the cellular and molec ... Full text Link to item Cite

Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities.

Journal Article iScience · October 21, 2022 Two prominent frontline breast cancer (BC) chemotherapies commonly used in combination, doxorubicin (DOX) and docetaxel (TAX), are associated with long-lasting cardiometabolic and musculoskeletal side effects. Whereas DOX has been linked to mitochondrial d ... Full text Open Access Link to item Cite

Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis.

Journal Article Cell Rep · August 16, 2022 Electron transport chain (ETC) biogenesis is tightly coupled to energy levels and availability of ETC subunits. Complex III (CIII), controlling ubiquinol:ubiquinone ratio in ETC, is an attractive node for modulating ETC levels during metabolic stress. Here ... Full text Link to item Cite

Proteomics and phosphoproteomics datasets of a muscle-specific STIM1 loss-of-function mouse model.

Journal Article Data Brief · June 2022 STIM1 is an ER/SR transmembrane protein that interacts with ORAI1 to activate store operated Ca2+ entry (SOCE) upon ER/SR depletion of calcium. Normally highly expressed in skeletal muscle, STIM1 deficiency causes significant changes to mitochondrial ultra ... Full text Link to item Cite

Mitochondrial lysine acylation and cardiometabolic stress: Truth or consequence?

Journal Article Curr Opin Physiol · June 2022 Disruptions in oxidative metabolism are often accompanied by tissue accumulation of catabolic carbon intermediates, including acyl CoA molecules that can react with the epsilon amino group of lysine residues on cellular proteins. In general, acyl-lysine po ... Full text Link to item Cite

Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.

Journal Article Sci Rep · May 6, 2022 Rheumatoid arthritis (RA) T cells drive autoimmune features via metabolic reprogramming that reduces oxidative metabolism. Exercise training improves cardiorespiratory fitness (i.e., systemic oxidative metabolism) and thus may impact RA T cell oxidative me ... Full text Open Access Link to item Cite

Disruption of STIM1-mediated Ca2+ sensing and energy metabolism in adult skeletal muscle compromises exercise tolerance, proteostasis, and lean mass.

Journal Article Mol Metab · March 2022 OBJECTIVE: Stromal interaction molecule 1 (STIM1) is a single-pass transmembrane endoplasmic/sarcoplasmic reticulum (E/SR) protein recognized for its role in a store operated Ca2+ entry (SOCE), an ancient and ubiquitous signaling pathway. Whereas STIM1 is ... Full text Open Access Link to item Cite

Nicotinamide riboside supplementation confers marginal metabolic benefits in obese mice without remodeling the muscle acetyl-proteome.

Journal Article iScience · January 21, 2022 Nicotinamide riboside supplements (NRS) have been touted as a nutraceutical that promotes cardiometabolic and musculoskeletal health by enhancing nicotinamide adenine dinucleotide (NAD+) biosynthesis, mitochondrial function, and/or the activities of NAD-de ... Full text Link to item Cite

Desmin interacts with STIM1 and coordinates Ca2+ signaling in skeletal muscle.

Journal Article JCI Insight · September 8, 2021 Stromal interaction molecule 1 (STIM1), the sarcoplasmic reticulum (SR) transmembrane protein, activates store-operated Ca2+ entry (SOCE) in skeletal muscle and, thereby, coordinates Ca2+ homeostasis, Ca2+-dependent gene expression, and contractility. STIM ... Full text Open Access Link to item Cite

Myocardial Lipin 1 knockout in mice approximates cardiac effects of human LPIN1 mutations.

Journal Article JCI Insight · May 10, 2021 Lipin 1 is a bifunctional protein that is a transcriptional regulator and has phosphatidic acid (PA) phosphohydrolase activity, which dephosphorylates PA to generate diacylglycerol. Human lipin 1 mutations lead to episodic rhabdomyolysis, and some affected ... 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

Nutritional modulation of heart failure in mitochondrial pyruvate carrier-deficient mice.

Journal Article Nat Metab · November 2020 The myocardium is metabolically flexible; however, impaired flexibility is associated with cardiac dysfunction in conditions including diabetes and heart failure. The mitochondrial pyruvate carrier (MPC) complex, composed of MPC1 and MPC2, is required for ... Full text Link to item Cite

Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure.

Journal Article Circ Res · September 25, 2020 RATIONALE: Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains ... Full text Link to item Cite

Voices: Meet the Advisory Board.

Journal Article Cell Metab · June 2, 2020 We are excited to announce that the Cell Metabolism Advisory Board has grown to better represent the metabolism community. We are honored to present these leaders as they share their perspectives. From taking unexpected journeys to pushing for a stronger f ... Full text Link to item Cite

Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury.

Journal Article Cell Metab · March 3, 2020 Continual efferocytic clearance of apoptotic cells (ACs) by macrophages prevents necrosis and promotes injury resolution. How continual efferocytosis is promoted is not clear. Here, we show that the process is optimized by linking the metabolism of engulfe ... Full text Link to item Cite

Disruption of Acetyl-Lysine Turnover in Muscle Mitochondria Promotes Insulin Resistance and Redox Stress without Overt Respiratory Dysfunction.

Journal Article Cell Metab · January 7, 2020 This study sought to examine the functional significance of mitochondrial protein acetylation using a double knockout (DKO) mouse model harboring muscle-specific deficits in acetyl-CoA buffering and lysine deacetylation, due to genetic ablation of carnitin ... Full text Link to item Cite

Rejuvenation of Neutrophil Functions in Association With Reduced Diabetes Risk Following Ten Weeks of Low-Volume High Intensity Interval Walking in Older Adults With Prediabetes - A Pilot Study.

Journal Article Front Immunol · 2020 Neutrophil dysfunction is a common feature of aging, and is associated with the pathogenesis of many age-related diseases, including type 2 diabetes mellitus (T2DM). Although exercise training improves metabolic health, decreases risk of T2DM, and is assoc ... Full text Link to item Cite

Gene Expression Differences In Three-dimensional Myobundles Compared To Two-dimensional Myocultures

Conference MEDICINE & SCIENCE IN SPORTS & EXERCISE · 2020 Cite

High-Intensity Interval Training Increases Rheumatoid Arthritis Cardiorespiratory Fitness in Association with Improvements in CD4+T Cell and Skeletal Muscle Mitochondrial Metabolism

Conference ARTHRITIS & RHEUMATOLOGY · 2020 Cite

Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.

Journal Article EBioMedicine · November 2019 BACKGROUND: Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose to ... Full text Link to item Cite

Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency.

Journal Article Cardiovasc Res · September 1, 2019 AIMS: The failing heart is energy-starved and inefficient due to perturbations in energy metabolism. Although ketone oxidation has been shown recently to increase in the failing heart, it remains unknown whether this improves cardiac energy production or e ... Full text Link to item Cite

Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity.

Journal Article Cell Metab · May 7, 2019 Crosstalk between metabolic and survival pathways is critical for cellular homeostasis, but the connectivity between these processes remains poorly defined. We used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of infl ... Full text Link to item Cite

Electrical stimulation increases hypertrophy and metabolic flux in tissue-engineered human skeletal muscle.

Journal Article Biomaterials · April 2019 In vitro models of contractile human skeletal muscle hold promise for use in disease modeling and drug development, but exhibit immature properties compared to native adult muscle. To address this limitation, 3D tissue-engineered human muscles (myobundles) ... Full text Link to item Cite

Mitochondrial Driving Forces and Metabolic Resilience

Conference FASEB JOURNAL · April 1, 2019 Link to item Cite

Abstract P284: The Chemotherapeutic Agent Docetaxel Disrupts Mitochondrial Energetics in 3D Human Bioengineered Myobundles

Conference Circulation · March 5, 2019 Taxanes (i.e. docetaxel, (TAX)) comprise the first line-treatment for breast cancer (BC), mostly in combination with anthracyclines like doxorubicin (DOX). The efficacy of these drugs as antineoplastic agents has helped to boost 10-yea ... Full text Cite

Creation of versatile cloning platforms for transgene expression and dCas9-based epigenome editing.

Journal Article Nucleic Acids Res · February 28, 2019 Genetic manipulation via transgene overexpression, RNAi, or Cas9-based methods is central to biomedical research. Unfortunately, use of these tools is often limited by vector options. We have created a modular platform (pMVP) that allows a gene of interest ... Full text Link to item Cite

A fast and sensitive method combining reversed-phase chromatography with high resolution mass spectrometry to quantify 2-fluoro-2-deoxyglucose and its phosphorylated metabolite for determining glucose uptake

Journal Article ChemRxiv · February 27, 2019 Full text Link to item Cite

The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense.

Journal Article JCI Insight · February 21, 2019 Evidence has emerged that the failing heart increases utilization of ketone bodies. We sought to determine whether this fuel shift is adaptive. Mice rendered incapable of oxidizing the ketone body 3-hydroxybutyrate (3OHB) in the heart exhibited worsened he ... Full text Link to item Cite

Respiratory Phenomics across Multiple Models of Protein Hyperacylation in Cardiac Mitochondria Reveals a Marginal Impact on Bioenergetics.

Journal Article Cell Rep · February 5, 2019 Acyl CoA metabolites derived from the catabolism of carbon fuels can react with lysine residues of mitochondrial proteins, giving rise to a large family of post-translational modifications (PTMs). Mass spectrometry-based detection of thousands of acyl-PTMs ... Full text Link to item Cite

High Intensity Interval Training Improves Rheumatoid Arthritis Cardiorespiratory Fitness and Systemic Inflammation in Association with Alterations in Skeletal Muscle Metabolomic Profiles

Conference ARTHRITIS & RHEUMATOLOGY · 2019 Cite

Increasing fatty acid oxidation in the failing heart does not improve cardiac function

Conference Journal of Molecular and Cellular Cardiology · November 2018 Full text Cite

Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2018 High concentrations of propionate and its metabolites are found in several diseases that are often associated with the development of cardiac dysfunction, such as obesity, diabetes, propionic acidemia, and methylmalonic acidemia. In the present work, we em ... Full text Link to item Cite

Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes.

Journal Article Cell Rep · September 25, 2018 Chronic metabolic diseases have been linked to molecular signatures of mitochondrial dysfunction. Nonetheless, molecular remodeling of the transcriptome, proteome, and/or metabolome does not necessarily translate to functional consequences that confer phys ... Full text 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

Metabolomic analysis of insulin resistance across different mouse strains and diets.

Journal Article J Biol Chem · November 24, 2017 Insulin resistance is a major risk factor for many diseases. However, its underlying mechanism remains unclear in part because it is triggered by a complex relationship between multiple factors, including genes and the environment. Here, we used metabolomi ... Full text Link to item Cite

Bicarbonate alters cellular responses in respiration assays.

Journal Article Biochem Biophys Res Commun · August 5, 2017 Metabolic assay buffers often omit bicarbonate, which is susceptible to alkalinisation in an open environment. Here, we assessed the effect of including bicarbonate in respirometry experiments. By supplementing HEPES-buffered media with low concentrations ... Full text Link to item Cite

Cardiac Deletion of the Mitochondrial Pyruvate Carrier Results in Dilated Cardiomyopathy with Preservation of Fatty Acid Catabolism

Conference CIRCULATION RESEARCH · July 21, 2017 Link to item Cite

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion.

Journal Article Cell Metab · April 4, 2017 Sirtuins are NAD+-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control h ... Full text Link to item Cite

HDAC3 sets the timer on muscle fuel switching.

Journal Article Nat Med · February 7, 2017 Full text Link to item Cite

Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.

Journal Article Arthritis Res Ther · January 23, 2017 BACKGROUND: To identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA. METHODS: Persons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, bod ... Full text Open Access Link to item Cite

Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction.

Journal Article Biochem Biophys Res Commun · October 28, 2016 The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19-29 years) and fifteen middle-to older-aged (57-82 years) individuals underw ... Full text Link to item Cite

Comprehensive metabolic modeling of multiple 13C-isotopomer data sets to study metabolism in perfused working hearts.

Journal Article Am J Physiol Heart Circ Physiol · October 1, 2016 In many forms of cardiomyopathy, alterations in energy substrate metabolism play a key role in disease pathogenesis. Stable isotope tracing in rodent heart perfusion systems can be used to determine cardiac metabolic fluxes, namely those relative fluxes th ... Full text Link to item Cite

Regulation of Carnitine Acetyltransferase by Lysine Acetylation

Conference DIABETES · June 1, 2016 Link to item Cite

The Failing Heart Relies on Ketone Bodies as a Fuel.

Journal Article Circulation · February 23, 2016 Featured Publication BACKGROUND: Significant evidence indicates that the failing heart is energy starved. During the development of heart failure, the capacity of the heart to utilize fatty acids, the chief fuel, is diminished. Identification of alternate pathways for myocardi ... Full text Link to item Cite

Mitochondrial protein hyperacetylation in the failing heart.

Journal Article JCI Insight · February 2016 Featured Publication Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothe ... Full text Link to item Cite

The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins.

Journal Article Cell Rep · January 12, 2016 Featured Publication Lysine acetylation (AcK), a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitoch ... Full text 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

Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle.

Journal Article EBioMedicine · November 2015 Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non-hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that ... Full text Link to item Cite

ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate.

Journal Article PLoS Genet · October 2015 In order to propagate a solid tumor, cancer cells must adapt to and survive under various tumor microenvironment (TME) stresses, such as hypoxia or lactic acidosis. To systematically identify genes that modulate cancer cell survival under stresses, we perf ... Full text Open Access Link to item Cite

Increased palmitate intake: higher acylcarnitine concentrations without impaired progression of β-oxidation.

Journal Article J Lipid Res · September 2015 Palmitic acid (PA) is associated with higher blood concentrations of medium-chain acylcarnitines (MCACs), and we hypothesized that PA may inhibit progression of FA β-oxidation. Using a cross-over design, 17 adults were fed high PA (HPA) and low PA/high ole ... Full text Link to item Cite

SIRT3 Directs Carbon Traffic in Muscle to Promote Glucose Control.

Journal Article Diabetes · September 2015 Full text Link to item Cite

Abstract 3004: Contextual RNAi screen identifies ACLY and ACC1 as mediators of hypoxia-induced apoptosis through metabolic and transcriptional mechanisms

Conference Cancer Research · August 1, 2015 AbstractTo become established as a solid tumor, cancer cells must adapt to and survive under various tumor microenvironment (TME) stresses, such as hypoxia or lactic acidosis. While many stress-signaling mec ... Full text Cite

Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative.

Journal Article Circ Res · July 17, 2015 Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level ... Full text Link to item Cite

Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.

Journal Article Cell Metab · July 7, 2015 The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress i ... Full text Link to item Cite

Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise.

Journal Article Cell Metab · July 7, 2015 Featured Publication Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding ... Full text Link to item Cite

Women in metabolism: part I.

Journal Article Cell Metab · May 5, 2015 In continuing our 10th anniversary celebrations, we asked women scientists in the metabolism field to share their stories and words of wisdom for the new generation and are happy to present the first 12 Voices of our "Women in Metabolism" series. ... Full text Link to item Cite

Muscle-Specific Overexpression of PGC-1α Does Not Augment Metabolic Improvements in Response to Exercise and Caloric Restriction.

Journal Article Diabetes · May 2015 Featured Publication This study used mice with muscle-specific overexpression of PGC-1α, a transcriptional coactivator that promotes mitochondrial biogenesis, to determine whether increased oxidative potential facilitates metabolic improvements in response to lifestyle modific ... Full text Link to item Cite

Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid handling in obese humans.

Journal Article Obesity (Silver Spring) · May 2015 OBJECTIVE: Investigate the effects of obesity and high-fat diet (HFD) exposure on fatty acid oxidation and TCA cycle intermediates and amino acids in skeletal muscle to better characterize energy metabolism. METHODS: Plasma and skeletal muscle metabolomic ... Full text Link to item Cite

Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid handling in obese humans

Journal Article Obesity · May 1, 2015 Objective Investigate the effects of obesity and high-fat diet (HFD) exposure on fatty acid oxidation and TCA cycle intermediates and amino acids in skeletal muscle to better characterize energy metabolism. Methods Plasma and skeletal muscle metabolomic pr ... Full text Cite

Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy-consuming redox circuit.

Journal Article Biochem J · April 15, 2015 Featured Publication Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+/NADH) and anabolic (NADP+/NADPH) processes integrate during metabolism to maintain cellular redox homoeostasis, howe ... Full text Link to item Cite

Compartmentalized acyl-CoA metabolism in skeletal muscle regulates systemic glucose homeostasis.

Journal Article Diabetes · January 2015 The impaired capacity of skeletal muscle to switch between the oxidation of fatty acid (FA) and glucose is linked to disordered metabolic homeostasis. To understand how muscle FA oxidation affects systemic glucose, we studied mice with a skeletal muscle-sp ... Full text Link to item Cite

Abstract PR09: A genome-wide RNAi screen reveals a protective role of decreased lipogenesis under hypoxia

Conference Cancer Research · January 1, 2015 AbstractAs solid tumors form, a number of physiological changes occur within the tumor, including low oxygen levels (hypoxia) and an accumulation of lactic acid with concomitant lowered pH levels (lactic aci ... Full text Cite

Diabetes: The good in fat.

Journal Article Nature · December 4, 2014 A new class of fatty acid — found in food and synthesized by mammalian tissues — enhances glucose uptake from the blood and reduces inflammation, suggesting that these fats might be used to treat diabetes. ... Full text Link to item Cite

Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock.

Journal Article Cell · December 4, 2014 Featured Publication Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. ... Full text Link to item Cite

Downregulation of carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion.

Journal Article Diabetes · November 2014 We previously demonstrated that micro-RNAs (miRNAs) 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of miRNAs 132 and 21 ... Full text Link to item Cite

Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.

Journal Article Diabetologia · November 2014 Featured Publication AIMS/HYPOTHESIS: Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. ... Full text Link to item Cite

Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.

Journal Article Circ Heart Fail · November 2014 Featured Publication BACKGROUND: An unbiased systems approach was used to define energy metabolic events that occur during the pathological cardiac remodeling en route to heart failure (HF). METHODS AND RESULTS: Combined myocardial transcriptomic and metabolomic profiling were ... Full text Link to item Cite

Long-echo time MR spectroscopy for skeletal muscle acetylcarnitine detection.

Journal Article J Clin Invest · November 2014 Animal models suggest that acetylcarnitine production is essential for maintaining metabolic flexibility and insulin sensitivity. Because current methods to detect acetylcarnitine involve biopsy of the tissue of interest, noninvasive alternatives to measur ... Full text Link to item Cite

Treatment with the 3-ketoacyl-CoA thiolase inhibitor trimetazidine does not exacerbate whole-body insulin resistance in obese mice.

Journal Article J Pharmacol Exp Ther · June 2014 There is a growing need to understand the underlying mechanisms involved in the progression of cardiovascular disease during obesity and diabetes. Although inhibition of fatty acid oxidation has been proposed as a novel approach to treat ischemic heart dis ... Full text Link to item Cite

A Transcriptomic Analysis of Responses to Overnight Fasting and Refeeding in the Human Skeletal Muscle

Journal Article ENDOCRINE REVIEWS · June 1, 2014 Link to item Cite

Obesity and lipid stress inhibit carnitine acetyltransferase activity.

Journal Article J Lipid Res · April 2014 Carnitine acetyltransferase (CrAT) is a mitochondrial matrix enzyme that catalyzes the interconversion of acetyl-CoA and acetylcarnitine. Emerging evidence suggests that this enzyme functions as a positive regulator of total body glucose tolerance and musc ... Full text Link to item Cite

Targeted metabolomics connects thioredoxin-interacting protein (TXNIP) to mitochondrial fuel selection and regulation of specific oxidoreductase enzymes in skeletal muscle.

Journal Article J Biol Chem · March 21, 2014 Featured Publication Thioredoxin-interacting protein (TXNIP) is an α-arrestin family member involved in redox sensing and metabolic control. Growing evidence links TXNIP to mitochondrial function, but the molecular nature of this relationship has remained poorly defined. Herei ... 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

A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.

Journal Article Circ Res · February 14, 2014 RATIONALE: Increasing evidence has shown that proper control of mitochondrial dynamics (fusion and fission) is required for high-capacity ATP production in the heart. Transcriptional coactivators, peroxisome proliferator-activated receptor γ coactivator-1 ... Full text Link to item Cite

Glycerol-3-phosphate acyltransferase (GPAT)-1, but not GPAT4, incorporates newly synthesized fatty acids into triacylglycerol and diminishes fatty acid oxidation.

Journal Article J Biol Chem · September 20, 2013 Four glycerol-3-phosphate acyltransferase (GPAT) isoforms, each encoded by a separate gene, catalyze the initial step in glycerolipid synthesis; in liver, the major isoforms are GPAT1 and GPAT4. To determine whether each of these hepatic isoforms performs ... Full text Link to item Cite

Erratum: Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood (American Journal of Clinical Nutrition (2013) 97 (689-697))

Journal Article American Journal of Clinical Nutrition · August 1, 2013 Full text Cite

Increased Muscle Mitochondrial Mass in MCK-PGC1 alpha Transgenic Mice Alters Metabolic Responses to Diet and Exercise Intervention But Does Not Improve Clinically Relevant Outcomes

Journal Article DIABETES · July 1, 2013 Link to item Cite

SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase.

Journal Article Mol Cell · June 6, 2013 Lipid metabolism is tightly controlled by the nutritional state of the organism. Nutrient-rich conditions increase lipogenesis, whereas nutrient deprivation promotes fat oxidation. In this study, we identify the mitochondrial sirtuin, SIRT4, as a regulator ... 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 Featured Publication 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

Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood.

Journal Article Am J Clin Nutr · April 2013 BACKGROUND: The Western diet increases risk of metabolic disease. OBJECTIVE: We determined whether lowering the ratio of saturated fatty acids to monounsaturated fatty acids in the Western diet would affect physical activity and energy expenditure. DESIGN: ... Full text Link to item Cite

Highlights of the 2012 Research Workshop: Using nutrigenomics and metabolomics in clinical nutrition research.

Journal Article JPEN J Parenter Enteral Nutr · March 2013 The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Research Workshop, "Using Nutrigenomics and Metabolomics in Clinical Nutrition Research," was held on January 21, 2012, in Orlando, Florida. The conference brought together experts in h ... Full text Link to item Cite

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans.

Journal Article J Lipid Res · February 2013 Featured Publication Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who ... Full text Link to item Cite

Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice.

Journal Article Am J Physiol Regul Integr Comp Physiol · February 2013 Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism ... Full text Link to item Cite

Genome-wide chromatin state transitions associated with developmental and environmental cues.

Journal Article Cell · January 31, 2013 Differences in chromatin organization are key to the multiplicity of cell states that arise from a single genetic background, yet the landscapes of in vivo tissues remain largely uncharted. Here, we mapped chromatin genome-wide in a large and diverse colle ... Full text Link to item Cite

Identification of a novel malonyl-CoA IC(50) for CPT-I: implications for predicting in vivo fatty acid oxidation rates.

Journal Article Biochem J · November 15, 2012 Published values regarding the sensitivity (IC(50)) of CPT-I (carnitine palmitoyltransferase I) to M-CoA (malonyl-CoA) inhibition in isolated mitochondria are inconsistent with predicted in vivo rates of fatty acid oxidation. Therefore we have re-examined ... Full text Link to item Cite

Revisiting the connection between intramyocellular lipids and insulin resistance: a long and winding road.

Journal Article Diabetologia · October 2012 In the mid-1990s, researchers began to re-examine type 2 diabetes from a more 'lipocentric' perspective; giving strong consideration to the idea that systemic lipid imbalances give rise to glucose dysregulation, rather than vice versa. At the forefront of ... Full text Link to item Cite

Diet Oleic Acid (OA) Improves Metabolic Risk Factors in Young Adults: Lipidomic Analysis of Sexually Dimorphic Responsiveness

Journal Article DIABETES · June 1, 2012 Link to item Cite

Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.

Journal Article Cell Metab · May 2, 2012 Featured Publication The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing reco ... Full text Link to item Cite

Lipid-induced mitochondrial stress and insulin action in muscle.

Journal Article Cell Metab · May 2, 2012 Featured Publication The interplay between mitochondrial energetics, lipid balance, and muscle insulin sensitivity has remained a topic of intense interest and debate for decades. One popular view suggests that increased oxidative capacity benefits metabolic wellness, based on ... Full text Link to item Cite

Caloric restriction, aerobic exercise or a combination improves metabolic profiles following diet-induced obesity

Journal Article FASEB JOURNAL · April 1, 2012 Link to item Cite

Distinct roles of specific fatty acids in cellular processes: implications for interpreting and reporting experiments.

Journal Article Am J Physiol Endocrinol Metab · January 1, 2012 Plasma contains a variety of long-chain fatty acids (FAs), such that about 35% are saturated and 65% are unsaturated. There are countless examples that show how different FAs impart specific and unique effects, or even opposing actions, on cellular functio ... Full text Link to item Cite

Caloric restriction, aerobic exercise or a combination improves metabolic profiles following diet-induced obesity

Conference FASEB JOURNAL · 2012 Cite

Re-patterning of skeletal muscle energy metabolism by fat storage-inducing transmembrane protein 2.

Journal Article J Biol Chem · December 9, 2011 Triacylglyceride stored in cytosolic lipid droplets (LDs) constitutes a major energy reservoir in most eukaryotes. The regulated turnover of triacylglyceride in LDs provides fatty acids for mitochondrial β-oxidation and ATP generation in physiological stat ... Full text Link to item Cite

Effects of Muscle Specific Deletion of Carnitine Palmitoyltransferase and Carnitine Acetyltransferase on Fuel Selection

Conference DIABETES · July 1, 2011 Link to item Cite

Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system.

Journal Article Diabetes · July 2011 Featured Publication OBJECTIVE: Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy hom ... Full text Link to item Cite

Mouse cardiac acyl coenzyme a synthetase 1 deficiency impairs Fatty Acid oxidation and induces cardiac hypertrophy.

Journal Article Mol Cell Biol · March 2011 Long-chain acyl coenzyme A (acyl-CoA) synthetase isoform 1 (ACSL1) catalyzes the synthesis of acyl-CoA from long-chain fatty acids and contributes the majority of cardiac long-chain acyl-CoA synthetase activity. To understand its functional role in the hea ... Full text Link to item Cite

A high-fat diet elicits differential responses in genes coordinating oxidative metabolism in skeletal muscle of lean and obese individuals.

Journal Article J Clin Endocrinol Metab · March 2011 CONTEXT: In lean individuals, increasing dietary lipid can elicit an increase in whole body lipid oxidation; however, with obesity the capacity to respond to changes in substrate availability appears to be compromised. OBJECTIVE: To determine whether the r ... Full text Link to item Cite

Short-term effects of dietary fatty acids on muscle lipid composition and serum acylcarnitine profile in human subjects.

Journal Article Obesity (Silver Spring) · February 2011 In cultured cells, palmitic acid (PA) and oleic acid (OA) confer distinct metabolic effects, yet, unclear, is whether changes in dietary fat intake impact cellular fatty acid (FA) composition. We hypothesized that short-term increases in dietary PA or OA w ... Full text Link to item Cite

Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption.

Journal Article Diabetes · October 2010 OBJECTIVE: It has been proposed that skeletal muscle insulin resistance arises from the accumulation of intramyocellular lipid metabolites that impede insulin signaling, including diacylglycerol and ceramide. We determined the role of de novo ceramide synt ... Full text Link to item Cite

Effects of High and Low Palmitic Acid Diets on Whole Body, Tissue, and Serum Lipids

Conference OBESITY · October 1, 2010 Link to item Cite

Effects of High and Low Palmitic Acid Diets on Fatty Acid Metabolism in Non-Obese Human Subjects

Conference OBESITY · October 1, 2010 Link to item Cite

Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.

Journal Article PLoS Genet · September 2, 2010 Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer c ... Full text Open Access Link to item Cite

Metabolic profiling of muscle contraction in lean compared with obese rodents.

Journal Article Am J Physiol Regul Integr Comp Physiol · September 2010 Featured Publication Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose ... Full text Link to item Cite

Metabolism and vascular fatty acid transport.

Journal Article N Engl J Med · July 15, 2010 Full text Link to item Cite

Adipose acyl-CoA synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis.

Journal Article Cell Metab · July 7, 2010 Long-chain acyl-CoA synthetase-1 (ACSL1) contributes 80% of total ACSL activity in adipose tissue and was believed to be essential for the synthesis of triacylglycerol. We predicted that an adipose-specific knockout of ACSL1 (Acsl1(A-/-)) would be lipodyst ... Full text Link to item Cite

Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression.

Journal Article J Clin Endocrinol Metab · July 2010 CONTEXT: Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance. OBJECTIVE: To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, ... Full text Link to item Cite

Alterations in skeletal muscle fatty acid handling predisposes middle-aged mice to diet-induced insulin resistance.

Journal Article Diabetes · June 2010 OBJECTIVE: Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to ... Full text Link to item Cite

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals.

Journal Article Diabetes · June 2010 OBJECTIVE: To determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxiso ... Full text Link to item Cite

Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction.

Journal Article Diabetes · May 2010 OBJECTIVE: Peripheral insulin resistance is linked to an increase in reactive oxygen species (ROS), leading in part to the production of reactive lipid aldehydes that modify the side chains of protein amino acids in a reaction termed protein carbonylation. ... Full text Link to item Cite

Loss of ovarian function alters multiple aspects of lipid metabolism in adipose tissue and skeletal muscle from female mice.

Journal Article FASEB JOURNAL · April 1, 2010 Link to item Cite

Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused?

Journal Article Biochim Biophys Acta · March 2010 The term lipotoxicity elicits visions of steatotic liver, fat laden skeletal muscles and engorged lipid droplets that spawn a number of potentially harmful intermediates that can wreak havoc on signal transduction and organ function. Prominent among these ... Full text Link to item Cite

Metabolomics applied to diabetes research: moving from information to knowledge.

Journal Article Diabetes · November 2009 Featured Publication Full text Link to item Cite

Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis and beta-oxidation and alters phospholipid fatty acid composition.

Journal Article J Biol Chem · October 9, 2009 In mammals, a family of five acyl-CoA synthetases (ACSLs), each the product of a separate gene, activates long chain fatty acids to form acyl-CoAs. Because the ACSL isoforms have overlapping preferences for fatty acid chain length and saturation and are ex ... Full text Link to item Cite

ALTERATIONS IN MITOCHONDRIAL FUEL METABOLISM AND SURVIVAL WITH REDUCED MANGANESE SUPEROXIDE DISMUTASE (SOD2)

Journal Article GERONTOLOGIST · October 1, 2009 Link to item Cite

Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control.

Journal Article J Biol Chem · August 21, 2009 Featured Publication In addition to its essential role in permitting mitochondrial import and oxidation of long chain fatty acids, carnitine also functions as an acyl group acceptor that facilitates mitochondrial export of excess carbons in the form of acylcarnitines. Recent e ... Full text Link to item Cite

Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase.

Journal Article Diabetes · August 2009 OBJECTIVE: Whereas an impaired ability to oxidize fatty acids is thought to contribute to intracellular lipid accumulation, insulin resistance, and cardiac dysfunction, high rates of fatty acid oxidation could also impair glucose metabolism and function. W ... Full text Link to item Cite

Increased insulin sensitivity in mice lacking collectrin, a downstream target of HNF-1alpha.

Journal Article Mol Endocrinol · June 2009 Collectrin is a downstream target of the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha), which is mutated in maturity-onset diabetes of the young subtype 3 (MODY3). Evidence from transgenic mouse models with collectrin overexpression in ... Full text Link to item Cite

Metabolic profiling of PPARalpha-/- mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation.

Journal Article FASEB J · February 2009 Featured Publication Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a master transcriptional regulator of beta-oxidation and a prominent target of hypolipidemic drugs. To gain deeper insights into the systemic consequences of impaired fat catabolism, we used q ... 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

Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase (Diabetes (2009) 58, (1766-1775))

Journal Article Diabetes · 2009 Featured Publication Cite

Insulin-Stimulated Glucose Oxidation is Increased in Hearts from High Fat Diet-Induced Obese Mice Lacking Malonyl CoA Decarboxylase

Journal Article CIRCULATION · October 28, 2008 Link to item Cite

Fatty acid oxidation and insulin action: when less is more.

Journal Article Diabetes · June 2008 Featured Publication Full text Link to item Cite

Metabolic crosstalk between human skeletal myocytes and co-cultured adipocytes

Conference DIABETES · June 1, 2008 Link to item Cite

Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression.

Journal Article Proc Natl Acad Sci U S A · May 13, 2008 Glucose is a fundamental metabolite, yet how cells sense and respond to changes in extracellular glucose concentration is not completely understood. We recently reported that the MondoA:Mlx dimeric transcription factor directly regulates glycolysis. In thi ... Full text Link to item Cite

Fatty acid transporter expression in human myocytes

Journal Article FASEB JOURNAL · April 1, 2008 Link to item Cite

Mechanisms of disease:Molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes.

Journal Article Nat Rev Mol Cell Biol · March 2008 Featured Publication Nearly unlimited supplies of energy-dense foods and technologies that encourage sedentary behaviour have introduced a new threat to the survival of our species: obesity and its co-morbidities. Foremost among the co-morbidities is type 2 diabetes, which is ... 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 Featured Publication 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