Journal ArticleNat Rev Cardiol · February 23, 2026
Heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasingly prevalent, interrelated conditions driven by the global rise in obesity and metabolic syndrome. Once viewed in isol ...
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ConferenceCirculation 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 ...
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ConferenceDiabetes · 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleNat 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 ...
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Journal ArticleCell 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 ...
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Journal ArticlebioRxiv · 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 ...
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Journal ArticlebioRxiv · 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 ...
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Journal ArticleCell · 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleCell 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: ...
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Journal ArticleCell 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleClin 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 ...
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ConferenceJCI 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 ...
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Journal ArticleMol 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 ...
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Journal ArticleiScience · 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleData 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 ...
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Journal ArticleCurr 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 ...
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Journal ArticleSci 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 ...
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Journal ArticleMol 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 ...
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Journal ArticleiScience · 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 ...
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Journal ArticleJCI 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleNat 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 ...
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Journal ArticleCirc 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleFront 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 ...
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Journal ArticleEBioMedicine · 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 ...
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Journal ArticleCardiovasc 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleBiomaterials · 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) ...
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ConferenceCirculation · 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 ...
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Journal ArticleNucleic 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 ...
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Journal ArticleJCI 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleJCI 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleBiochem 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleArthritis 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 ...
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Journal ArticleBiochem 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleCirculation · February 23, 2016
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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 ...
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Journal ArticleJCI Insight · February 2016
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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 ...
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Journal ArticleCell Rep · January 12, 2016
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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 ...
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Journal ArticlePLoS 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 ...
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Journal ArticleEBioMedicine · 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 ...
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Journal ArticlePLoS 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 ...
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Journal ArticleJ 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 ...
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ConferenceCancer 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 ...
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Journal ArticleCirc 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 ...
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Journal ArticleCell 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 ...
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Journal ArticleCell Metab · July 7, 2015
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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 ...
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Journal ArticleCell 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. ...
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Journal ArticleDiabetes · May 2015
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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 ...
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Journal ArticleObesity (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 ...
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Journal ArticleObesity · 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 ...
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Journal ArticleBiochem J · April 15, 2015
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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 ...
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Journal ArticleDiabetes · 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 ...
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ConferenceCancer 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 ...
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Journal ArticleNature · 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. ...
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Journal ArticleCell · December 4, 2014
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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. ...
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Journal ArticleDiabetes · 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 ...
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Journal ArticleDiabetologia · November 2014
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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. ...
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Journal ArticleCirc Heart Fail · November 2014
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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 ...
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Journal ArticleJ 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleJ Biol Chem · March 21, 2014
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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 ...
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Journal ArticleAm 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 ...
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Journal ArticleCirc 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleMol 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 ...
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Journal ArticleDiabetes · April 2013
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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 ...
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Journal ArticleAm 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: ...
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Journal ArticleJPEN 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 ...
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Journal ArticleJ Lipid Res · February 2013
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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 ...
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Journal ArticleAm 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 ...
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Journal ArticleCell · 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 ...
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Journal ArticleBiochem 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 ...
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Journal ArticleDiabetologia · 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 ...
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Journal ArticleCell Metab · May 2, 2012
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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 ...
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Journal ArticleCell Metab · May 2, 2012
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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 ...
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Journal ArticleAm 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleDiabetes · July 2011
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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 ...
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Journal ArticleMol 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleObesity (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 ...
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Journal ArticleDiabetes · 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 ...
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Journal ArticlePLoS 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 ...
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Journal ArticleAm J Physiol Regul Integr Comp Physiol · September 2010
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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 ...
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Journal ArticleCell 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 ...
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Journal ArticleJ 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, ...
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Journal ArticleDiabetes · 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 ...
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Journal ArticleDiabetes · 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 ...
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Journal ArticleDiabetes · 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. ...
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Journal ArticleBiochim 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleJ Biol Chem · August 21, 2009
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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 ...
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Journal ArticleDiabetes · 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 ...
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Journal ArticleMol 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 ...
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Journal ArticleFASEB J · February 2009
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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 ...
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Journal ArticleOMICS · 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 ...
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Journal ArticleProc 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 ...
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Journal ArticleNat Rev Mol Cell Biol · March 2008
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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 ...
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Journal ArticleCell Metab · January 2008
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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 ...
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Journal ArticleAppl Physiol Nutr Metab · October 2007
Dyslipidemia and intramuscular accumulation of fatty acid metabolites are increasingly recognized as core features of obesity and type 2 diabetes. Emerging evidence suggests that normal physiological adaptations to a heavy lipid load depend on the coordina ...
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Journal ArticleCell Metab · June 2007
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Thioredoxin-interacting protein (TXNIP) binds and inhibits the reducing activity of thioredoxin. A new study (Parikh et al., 2007) implicates this redox rheostat as a negative regulator of peripheral glucose metabolism in humans. Investigators combined hum ...
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Journal ArticleDiabetologia · April 2007
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AIMS/HYPOTHESIS: This study examined the efficacy of supplemental L: -carnitine as an adjunctive diabetes therapy in mouse models of metabolic disease. We hypothesised that carnitine would facilitate fatty acid export from tissues in the form of acyl-carni ...
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Journal ArticleAm J Physiol Cell Physiol · February 2007
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Acute exercise can reverse muscle insulin resistance, but the mechanism(s) of action are unknown. With the use of a hindlimb perfusion model, we have found that acute contraction restores insulin-stimulated glucose uptake in muscle of obese Zucker rats to ...
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Journal ArticleNovartis Found Symp · 2007
Insulin resistance is a hallmark of type 2 diabetes and commonly observed in other energy-stressed settings such as obesity, starvation, inactivity and ageing. Dyslipidaemia and 'lipotoxicity'--tissue accumulation of lipid metabolites-are increasingly reco ...
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Journal ArticleMol Cell · December 8, 2006
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In the absence of specific high-affinity agonists and antagonists, it has been difficult to define the target genes and biological responses attributable to many of the orphan nuclear receptors (ONRs). Indeed, it appears that many members of this receptor ...
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Journal ArticleAnnu Rev Biochem · 2006
An epidemic surge in the incidence of obesity has occurred worldwide over the past two decades. This alarming trend has been triggered by lifestyle habits that encourage overconsumption of energy-rich foods while also discouraging regular physical activity ...
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Journal ArticleCell Metab · October 2005
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Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA ...
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Journal ArticleJ Biol Chem · September 30, 2005
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Peroxisome proliferator-activated receptor-gamma co-activator 1alpha (PGC1alpha) is a promiscuous co-activator that plays a key role in regulating mitochondrial biogenesis and fuel homeostasis. Emergent evidence links decreased skeletal muscle PGC1alpha ac ...
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Journal ArticleJ Biol Chem · July 8, 2005
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In vitro studies suggest that the mitochondrial glycerol-3-phosphate acyltransferase-1 (mtGPAT1) isoform catalyzes the initial and rate-controlling step in glycerolipid synthesis and aids in partitioning acyl-CoAs toward triacylglycerol synthesis and away ...
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Journal ArticleAm J Physiol Cell Physiol · May 2005
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Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes ...
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Journal ArticleMed Sci Sports Exerc · April 2005
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PURPOSE: To examine noninsulin- (basal) and insulin-mediated glucose uptake in human skeletal muscle cells from endurance-trained and sedentary individuals. METHODS: Muscle biopsies (vastus lateralis) were obtained from competitive, endurance-trained athle ...
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Journal ArticleNat Med · March 2004
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Lipid infusion or ingestion of a high-fat diet results in insulin resistance, but the mechanism underlying this phenomenon remains unclear. Here we show that, in rats fed a high-fat diet, whole-animal, muscle and liver insulin resistance is ameliorated fol ...
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Journal ArticleBest Pract Res Clin Endocrinol Metab · December 2002
The adipocyte-derived hormone, leptin, regulates food intake and systemic fuel metabolism; ob /ob mice, which lack functional leptin, exhibit an obesity syndrome that is similar to morbid obesity in humans. Leptin receptors are expressed most abundantly in ...
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Journal ArticleJ Biol Chem · July 19, 2002
Ablation of peroxisome proliferator activated receptor (PPAR) alpha, a lipid-activated transcription factor that regulates expression of beta-oxidative genes, results in profound metabolic abnormalities in liver and heart. In the present study we used PPAR ...
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Journal ArticleAm J Physiol Endocrinol Metab · May 2002
Carnitine palmitoyltransferase I (CPT I), which is expressed as two distinct isoforms in liver (alpha) and muscle (beta), catalyzes the rate-limiting step in the transport of fatty acid into the mitochondria. Malonyl-CoA, a potent inhibitor of CPT I, is co ...
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Journal ArticleDiabetes · April 2002
In humans, skeletal muscle is a major site of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) expression, but its function in this tissue is unclear. We investigated the role of hPPAR-alpha in regulating muscle lipid utilization by studying t ...
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Journal ArticleAm J Physiol Endocrinol Metab · December 2000
Acyl-CoA synthetase (ACS) catalyzes the activation of long-chain fatty acids to acyl-CoAs, which can be metabolized to form CO(2), triacylglycerol (TAG), phospholipids (PL), and cholesteryl esters (CE). To determine whether inhibiting ACS affects these pat ...
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Journal ArticleJpn J Physiol · October 2000
In animals, female sex steroid hormones (SS, estrogens-progesterone) influence the energy substrate that is metabolized. Human research on this issue is controversial. This study examined whether changes in circulating SS hormone levels affected the carboh ...
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Journal ArticleJ Biol Chem · May 26, 2000
Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important rol ...
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Journal ArticleAnnu Rev Nutr · 2000
Although triacylglycerol stores play the critical role in an organism's ability to withstand fuel deprivation and are strongly associated with such disorders as diabetes, obesity, and atherosclerotic heart disease, information concerning the enzymes of tri ...
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ConferenceFertil Steril · June 1999
OBJECTIVE: To examine the interaction between circulating beta-endorphin levels and sex steroids during sustained submaximal exercise in runners who are either anovulatory and oligomenorrheic (AO) or ovulatory and eumenorrheic (EO). DESIGN: Controlled clin ...
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Journal ArticleAm J Physiol · May 1999
Because muscle triacylglycerol (TAG) accumulation might contribute to insulin resistance in leptin-deficient ob/ob mice, we studied the acute (60- to 90-min) effects of leptin and insulin on [14C]glucose and [14C]oleate metabolism in muscles isolated from ...
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Journal ArticleBiochem J · March 15, 1999
AMP-activated kinase (AMPK) is activated in response to metabolic stresses that deplete cellular ATP, and in both liver and skeletal muscle, activated AMPK stimulates fatty acid oxidation. To determine whether AMPK might reciprocally regulate glycerolipid ...
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Journal ArticleFASEB Journal · 1998
Activation of fatty acids by acyl-CoA synthetase (ACS) provides acyl-CoA for β-oxidation and for the synthesis of triacylglycerol (TAG), phospholipids (PL) and cholesterol esters (CE). Partitioning of acyl-CoAs towards these different metabolic fates is cr ...
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Journal ArticleFASEB Journal · December 1, 1997
Obesity and NIDDM are associated with increased plasma free fatty acids (FFA), hyperinsulinemia and elevated muscle triacylglycerol (TAG). We investigated: 1) the role of elevated FFA as a direct inhibitor of muscle glucose metabolism, and 2) the effects o ...
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Journal ArticleDiabetes · August 1997
Leptin, an adipocyte-derived hormone that directly regulates both adiposity and energy homeostasis, decreases food intake and appears to partition metabolic fuels toward utilization and away from storage. Because skeletal muscle expresses the leptin recept ...
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Journal ArticleJournal of Nutritional Biochemistry · January 1, 1997
Although skeletal muscle is recognized as a primary site of lipid utilization, the study of muscle bioenergetics has focused mainly on carbohydrate, and consequently our understanding of the variables that regulate muscle lipid metabolism is comparably poo ...
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Journal ArticleMed Sci Sports Exerc · January 1994
The present study examined the effects of dietary manipulations on six trained runners. The percent energy contributions from carbohydrate, fat, and protein were 61/24/14, 50/38/12, and 73/15/12 for the normal (N), fat (F), and carbohydrate (C) diets, resp ...
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