Lipid droplet dynamics and insulin sensitivity upon a 5-day high-fat diet in Caucasians and South Asians

摘要

A 5-day High-Fat High-Calorie diet (HFHC-diet) reduces insulin-stimulated glucose disposal (Rd) in South Asian, but not Caucasian healthy lean males. We aimed to investigate if differences in myocellular lipid handling are underlying this differential response. A two-step hyperinsulinemic-euglycemic clamp and muscle biopsies were performed in 12 healthy lean Caucasian and South Asian males (BMI??25?kg/m2, 19–25 years) before and after a 5-day HFHC-diet (regular diet?+?375?mL cream/day; 1275?kcal/day; 94% fat). Triglyceride extractions and Western Blots for lipid droplet and mitochondrial proteins were performed. Intramyocellular lipid content and HFHC-diet response were similar between ethnicities (group effect: P?=?0.094; diet effect: +~30%, P?=?0.044). PLIN5 protein content increased upon the HFHC-diet (P?=?0.031) and tended to be higher in South Asians (0.87?±?0.42?AU vs. 1.35?±?0.58?AU, P?=?0.07). 4-HNE tended to increase in South Asians upon the HFHC-diet (interaction effect: P?=?0.057). In Caucasians ΔPLIN5 content correlated with ΔRd (Caucasians: r?=?0.756, P?=?0.011; South Asians: r?=??0.085, P?=?0.816), while in South Asians Δ4-HNE associated with ΔPLIN5 content (Caucasians: r?=?0.312, P?=?0.380; South Asians: r?=?0.771, P?=?0.003). These data indicate that in Caucasians, PLIN5 may be protective against HFHC-diet induced insulin resistance, which for reasons not yet understood is not observed in South Asians, who possess increased lipid peroxidation levels.