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High-protein (HP) intake during weight loss (WL) therapy is often recommended because it reduces the loss of lean tissue mass. However, HP intake could have adverse effects on metabolic function, because protein ingestion reduces postprandial insulin sensitivity. In this study, we compared the effects of ∼10% WL with a hypocaloric diet containing 0.8 g protein/kg/day and a hypocaloric diet containing 1.2 g protein/kg/day on muscle insulin action in postmenopausal women with obesity. We found that HP intake reduced the WL-induced decline in lean tissue mass by ∼45%. However, HP intake also prevented the WL-induced improvements in muscle insulin signaling and insulin-stimulated glucose uptake, as well as the WL-induced adaptations in oxidative stress and cell structural biology pathways. Our data demonstrate that the protein content of a WL diet can have profound effects on metabolic function and underscore the importance of considering dietary macronutrient composition during WL therapy for people with obesity.

Type 2 diabetes mellitus (T2DM) is associated with increased plasma triglyceride (TG) concentrations, but African Americans (AA) have lower plasma TG than Caucasians (CC). We evaluated the hypothesis that obese AA women have lower plasma TG than obese CC women do because of differences in lipid kinetics. Eleven AA and 11 CC obese women with T2DM, matched on body mass index (BMI) (AA = 37 ± 1, CC = 37 ± 1 kg/m2), age, duration of diabetes, percentage body fat, and insulin sensitivity (SI, determined by an intravenous glucose tolerance test), were studied. Plasma TG concentration (AA = 1.14 ± 0.11, CC = 1.88 ± 0.18 mmol/l), FFA rate of appearance (Ra) into plasma (AA = 419 ± 27, CC = 503 ± 31 µmol·min−1), and total VLDL-TG secretion rate (AA = 18 ± 2, CC = 29 ± 4 µmol·min−1) were lower in AA than CC women (all P < 0.05). In contrast, plasma total apolipoprotein (apo)B-100 concentration (AA = 1,542 ± 179, CC = 1,620 ± 118 nmol/l) and VLDL-apoB-100 secretion rate (AA = 1.3 ± 0.1, CC = 1.3 ± 0.1 nmol·min−1) were similar in both groups, so the molar ratio of VLDL-TG secretion rate to VLDL-apoB-100 secretion rate was lower in AA women than in CC women. VLDL-TG concentration was lower in AA women due to lower total VLDL-TG secretion rate. However, the VLDL-apoB-100 secretion rate was the same in both groups, demonstrating that AA women secrete smaller VLDL particles containing less TG than do CC women.