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Branched-chain amino acids in metabolic signalling and insulin resistance
Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review, and a BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Expand
Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women.
Results are consistent with the working hypothesis that inefficient tissue LCFA beta-oxidation, due in part to a relatively low tricarboxylic acid cycle capacity, increases tissue accumulation of acetyl-CoA and generates chain-shortened acylcarnitine molecules that activate proinflammatory pathways implicated in insulin resistance. Expand
Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes.
Treatment with FGF19 prevented or reversed the diabetes that develops in mice made obese by genetic ablation of brown adipose tissue or genetic absence of leptin, and profiled the F GF19-induced gene expression changes in the liver and brown fat. Expand
Plasma Metabolomic Profiles Reflective of Glucose Homeostasis in Non-Diabetic and Type 2 Diabetic Obese African-American Women
This work examined differences in plasma concentrations of >350 metabolites in fasted obese T2DM vs. obese non-diabetic African-American women, and utilized principal components analysis to identify 158 metabolite components that strongly correlated with fasting HbA1c over a broad range of the latter. Expand
Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state.
  • S. Adams
  • Biology, Medicine
  • Advances in nutrition
  • 1 November 2011
A model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). Expand
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S]
These results and additional studies with the LPS sequester polymixin B and in MyD88−/− macrophages indicated that SFA-induced activation of TLR2 or TLR4 is a fatty acid-specific effect, but not due to contaminants in BSA or fatty acid preparations. Expand
UCP4, a novel brain‐specific mitochondrial protein that reduces membrane potential in mammalian cells
Findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain. Expand
Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses.
In obese subjects, consumption of fructose-sweetened beverages with meals was associated with less insulin secretion, blunted diurnal leptin profiles, and increased postprandial TG concentrations compared with glucose consumption, suggesting that fructose consumption may exacerbate an already adverse metabolic profile present in many obese subjects. Expand
Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity.
The hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT could impair WAT BCAA utilization is supported and mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals. Expand
PYY[3-36] administration decreases the respiratory quotient and reduces adiposity in diet-induced obese mice.
Negative energy balance after PYY[3-36] administration in diet-induced obese mice results from reduced food intake with a relative maintenance of mass-specific energy expenditure andFat loss and reduced RQ highlight the potential for PYY,[3- 36] to drive increased mobilization of fat stores to help meet energy requirements in this model. Expand