Acute Exposure to High-Fat Diets Increases Hepatic Expression of Genes Related to Cell Repair and Remodeling in Female Rats

Colette N. Miller
Heidi P. Morton
Paula T. Cooney
Tricia G. Winters
Keshia R. Ramseur
Srujana Rayalam, Philadelphia College of Osteopathic Medicine
Mary Anne Della-Fera
Clifton A. Baile
Lynda M. Brown

This article was published in Nutrition Research, Volume 34, Issue 1, January 2014, Pages 85-93.

The published version is available at http://dx.doi.org/10.1016/j.nutres.2013.10.010

Copyright © 2014 Elsevier B.V.

Abstract

High-fat diets (HFD) promote the development of both obesity and fatty liver disease through the up-regulation of hepatic lipogenesis. Insulin resistance, a hallmark of both conditions, causes dysfunctional fuel partitioning and increases in lipogenesis. Recent work has demonstrated that systemic insulin resistance occurs in as little as the first 72 hours of an HFD, suggesting the potential for hepatic disruption with HFD at this time point. The current study sought to determine differences in expression of lipogenic genes between sexes in 3-month-old male and female Long-Evans rats after 72 hours of a 40% HFD or a 17% fat (chow) diet. Owing to the response of estrogen on hepatic signaling, we hypothesized that a sexual dimorphic response would occur in the expression of lipogenic enzymes, inflammatory cytokines, apoptotic, and cell repair and remodeling genes. Both sexes consumed more energy when fed an HFD compared with their low fat-fed controls. However, only the males fed the HFD had a significant increase in body fat. Regardless of sex, HFD caused down-regulation of lipogenic and inflammatory genes. Interestingly, females fed an HFD had up-regulated expression of apoptotic and cell repair-related genes compared with the males. This may suggest that females are more responsive to the acute hepatic injury effects caused by HFDs. In summary, neither male nor female rats displayed disrupted hepatic metabolic pathways after 72 hours of the HFD treatment. In addition, female rats appear to have protection from increases in fat deposition, possibly due to increased caloric expenditure; male rats fed an HFD were less active, as demonstrated by distance traveled in their home cage.