Timothy Robert Koves

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

Skeletal muscle adaptation to fatty acid depends on coordinated actions of the PPARs and PGC1 alpha: implications for metabolic disease.

Journal article Appl Physiol Nutr Metab · October 2007 Featured Publication 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 ... 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

Lipid-induced metabolic dysfunction in skeletal muscle.

Journal article Novartis Found Symp · 2007 Featured Publication 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 ... 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

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

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

Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle.

Journal article Am J Physiol Endocrinol Metab · May 2002 Featured Publication 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 ... Full text Link to item Cite

Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in middle-aged men.

Journal article Am J Physiol Endocrinol Metab · January 2002 Featured Publication The purpose of this study was to determine whether the improved insulin action with short-term exercise training in middle-aged individuals is associated with enhanced phosphatidylinositol (PI) 3-kinase activity in skeletal muscle. Nine men of ages 50-70 y ... Full text Link to item Cite