Short‐term high‐fat diet impairs regulation of hepatic lipogenesis in rats

Abstract

Chronic high‐fat intake can produce obesity, fatty liver, and insulin resistance in rodents. We have found that a long‐term (>; 10 wk) high‐fat diet impairs the induction of SREBP‐1c and lipogenic enzymes by carbohydrate feeding. The present study investigated the early effects of the same diet on male Sprague Dawley rats consuming either a low‐fat (LF, 15%kcal, N=6) or a high‐fat (HF, 55% N=6) diet ad libitum for 1 wk. Although body weights were similar, HF rats had higher body fat (p< 0.02), liver lipid concentration (p< 0.02), and HOMA (p< 0.05 ) than LF rats. Analysis of liver samples collected from either 24 h food deprived rats or rats refed a high‐carbohydrate (55% kcal) diet for 16 hr, showed that refeeding increased mRNA for SREBP‐1c (10X), Acetyl CoA Carboxylase (7X), Fatty Acid Synthase (40X) and Pyruvate Kinase (6X) in LF, but only by 1.5 ‐ 3X in HF livers. Despite similar plasma insulin responses, LF showed greater feeding‐induced increases than HF in hepatic mTORC1 activity (increased p‐S6/total S6), and SREBP‐1c maturation, both mediators of insulin‐stimulated lipogenesis. Refeeding increased Fatty Acid Synthase protein content similarly in HF and LF at wk1, but did not do so at wk 10. These findings show that even short‐term HF diets impair early events in carbohydrate‐induced hepatic lipogenesis. NIH 1SC3GM086298