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Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets.(More)
In nonobese diabetic mice with uncontrolled type 1 diabetes, leptin therapy alone or combined with low-dose insulin reverses the catabolic state through suppression of hyperglucagonemia. Additionally, it mimics the anabolic actions of insulin monotherapy and normalizes hemoglobin A1c with far less glucose variability. We show that leptin therapy, like(More)
Integration of genetic and metabolic profiling holds promise for providing insight into human disease. Coronary artery disease (CAD) is strongly heritable, but the heritability of metabolomic profiles has not been evaluated in humans. We performed quantitative mass spectrometry-based metabolic profiling in 117 individuals within eight multiplex families(More)
Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. We selected 263 non-obese (BMI approximately 24 kg/m2) Asian-Indian and Chinese men from a large cross-sectional study(More)
Patients taking atypical antipsychotics are frequented by serious metabolic (eg, hyperglycemia, obesity, and diabetes) and cardiac effects. Surprisingly, chronic treatment also appears to lower free fatty acids (FFAs). This finding is paradoxical because insulin resistance is typically associated with elevated not lower FFAs. How atypical antipsychotics(More)
Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, β-hydroxybutyrate, ketones, insulin and glucose were performed in(More)
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 composition, metabolic rate, hormones, and 80 intermediary metabolites measured by mass spectrometry. In(More)
Gluconeogenesis makes a major contribution to hepatic glucose production, a process critical for survival in mammals. In this study, we identify the p160 family member, SRC-1, as a key coordinator of the hepatic gluconeogenic program in vivo. SRC-1-null mice displayed hypoglycemia secondary to a deficit in hepatic glucose production. Selective re-expression(More)
OBJECTIVE To understand relationships between exercise training-mediated improvements in insulin sensitivity (S(I)) and changes in circulating concentrations of metabolic intermediates, hormones, and inflammatory mediators. RESEARCH DESIGN AND METHODS Targeted mass spectrometry and enzyme-linked immunosorbent assays were used to quantify metabolic(More)