Ethnic and sex differences in hepatic lipid content and related cardiometabolic parameters in lean individuals

BACKGROUND: Nonalcoholic fatty liver affects 25% to 30% of the US and European populations; is associated with insulin resistance (IR), type 2 diabetes, and increased cardiovascular risk; and is defined by hepatic triglyceride (HTG) content greater than 5.56%. However, it is unknown whether HTG content less than 5.56% is associated with cardiometabolic risk factors and whether there are ethnic (Asian Indian, AI, versus non-AI) and/or sex differences in these parameters in lean individuals. METHODS: We prospectively recruited 2331 individuals and measured HTG, using (1)H magnetic resonance spectroscopy, and plasma concentrations of triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and uric acid. Insulin sensitivity was assessed using Homeostatic Model Assessment of Insulin Resistance and the Matsuda Insulin Sensitivity Index. RESULTS: The 95th percentile for HTG in lean non-AI individuals was 1.85%. Plasma insulin, triglycerides, total cholesterol, LDL-cholesterol, and uric acid concentrations were increased and HDL-cholesterol was decreased in individuals with HTG content > 1.85% and ≤ 5.56% compared with those individuals with HTG content ≤ 1.85%, and these altered parameters were associated with increased IR. Mean HTG was lower in lean non-AI women compared with lean non-AI men, whereas lean AI men and women had a 40% to 100% increase in HTG when compared with non-AI men and women, which was associated with increased cardiometabolic risk factors. CONCLUSION: We found that the 95th percentile of HTG in lean non-AI individuals was 1.85% and that HTG concentrations above this threshold were associated with IR and cardiovascular risk factors. Premenopausal women were protected from these changes whereas young, lean AI men and women manifested increased HTG content and associated cardiometabolic risk factors. FUNDING: Grants from the United States Department of Health and Human Resources (NIH/National Institute of Diabetes and Digestive and Kidney Diseases): R01 DK113984, P30 DK45735, U24 DK59635, and UL1 RR024139; and the Novo Nordisk Foundation (NNF18CC0034900).