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Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m 2 ] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1- 13 C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m 2 ) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher ( P &lt; 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 ( P = 0.06) and ceramide C16:0 ( P &lt; 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.

Effect of acute and short-term dietary fat ingestion on postprandial skeletal muscle protein synthesis rates in middle-aged, overweight, and obese men