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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 recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained(More)
In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is responsible for the first and rate-limiting step in the conversion of nicotinamide to nicotinamide adenine dinucleotide (NAD+). NAD+ is an obligate cosubstrate for mammalian sirtuin-1 (SIRT1), a deacetylase that activates peroxisome proliferator-activated receptor-gamma coactivator-1alpha(More)
The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of(More)
CONTEXT Obesity and type 2 diabetes are associated with elevated intramyocellular lipids (IMCLs) and insulin resistance. OBJECTIVE We tested the hypothesis that skeletal muscle lipases activity could influence IMCL content (including diacylglycerol and ceramides). DESIGN AND PATIENTS The present study included 48 subjects with a wide range of age (19-68(More)
OBJECTIVE The objective of this study was to determine the role of maximum mitochondrial capacity on the variation in insulin sensitivity within a population of patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Fifty-eight participants enrolled in a cross-sectional design: eight active controls [maximum aerobic capacity (VO(2max))(More)
OBJECTIVE This study investigated the disparity between muscle metabolic rate and mitochondrial metabolism in human muscle of sedentary vs. active individuals. RESEARCH DESIGN AND METHODS Chronic activity level was characterized by a physical activity questionnaire and a triaxial accelerometer as well as a maximal oxygen uptake test. The ATP and O(2)(More)
The purpose of this study was to investigate the influence of exercise training on intramyocellular lipid (IMCL) content and test the hypothesis that the effect of endurance-oriented exercise training on IMCL is dependent on characteristics of the population studied. Lean (N = 11, body mass index (BMI) = 22.2 ± 0.7 kg·m⁻²), obese (N = 14, BMI = 38.8 ± 1.7(More)
Increased intramyocellular triglyceride (IMTG) content is found in both insulin-sensitive endurance-trained subjects and insulin-resistant obese/type 2 diabetic subjects. A high turnover rate of the IMTG pool in athletes is proposed to reduce accumulation of lipotoxic intermediates interfering with insulin signaling. IMTG turnover is a composite measure of(More)
CONTEXT Aging is associated with insulin resistance and unfavorable changes in body composition including increased fat accumulation, particularly in visceral and ectopic depots. Recent studies suggest that skeletal muscle mitochondrial activity may underlie some age-associated metabolic abnormalities. OBJECTIVE Our objective was to measure mitochondrial(More)
OBJECTIVE Disturbances in lipid metabolism are strongly associated with insulin resistance and type 2 diabetes (T2D). We hypothesized that activation of cAMP/PKA and calcium signaling pathways in cultured human myotubes would provide further insight into regulation of lipid storage, lipolysis, lipid oxidation and insulin responsiveness. METHODS Human(More)