Scholars@Duke
Deborah Marie Muoio

Deborah Marie Muoio

George Barth Geller Distinguished Professor of Cardiovascular Disease
Medicine, Endocrinology, Metabolism, and Nutrition
muoio@duke.edu
Duke Box 104775, Durham, NC 27710
300 North Duke Street, Durham, NC 27701

Featured Works

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Journal article Diabetes · June 2008 Featured Publication Full text 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

TXNIP links redox circuitry to glucose control.

Journal article Cell Metab · June 2007 Featured Publication 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 ... Full text Link to item Cite

Carnitine revisited: potential use as adjunctive treatment in diabetes.

Journal article Diabetologia · April 2007 Featured Publication 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 ... Full text Link to item Cite

Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism.

Journal article Am J Physiol Cell Physiol · February 2007 Featured Publication 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 ... Full text Link to item Cite

Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs.

Journal article Mol Cell · December 8, 2006 Featured Publication 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 ... Full text Link to item Cite

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

Journal article Cell Metab · October 2005 Featured Publication 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 ... Full text Link to item Cite

Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency.

Journal article J Biol Chem · September 30, 2005 Featured Publication 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 ... Full text Link to item Cite

Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs.

Journal article J Biol Chem · July 8, 2005 Featured Publication 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 ... Full text Link to item Cite

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism.

Journal article Am J Physiol Cell Physiol · May 2005 Featured Publication 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 ... Full text Link to item Cite

Glucose uptake in muscle cell cultures from endurance-trained men.

Journal article Med Sci Sports Exerc · April 2005 Featured Publication 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 ... Full text Link to item Cite

Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance.

Journal article Nat Med · March 2004 Featured Publication 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 ... Full text Link to item Cite