Effects of Dietary Butyrate on Diet-Induced Obesity and Lipid Metabolism

Abstract

Abstract Objectives We examined the effects of dietary butyrate, a short-chain fatty acids (SCFAs) on body weight control and metabolism in a diet-induced obesity rat model. Methods Male Sprague-Dawley rats fed with high-fat diet for 14 weeks. Sodium butyrate was administrated through diet supplementation at 3% wt/wt for long-term (14 weeks) or drinking water at 1% for short-term (2 weeks). Serum and feces were collected. Colon and liver tissues used for analyzing mRNA expression. To assess the effects of butyrate on lipid metabolism, 3T3-L1 cells were treated with sodium butyrate and sodium-3-hyroxybutyrate during adipogenic differentiation. Results On the high-fat diet, dietary supplementation of butyrate protected against body weight gain. Interestingly, food intake was increased and consistently colonic Proglucagon (Gcg), encoding Glucagon-like Peptide-1 (GLP-1) involved in appetite-suppression, was decreased. In contrast, short-term administration of butyrate did not affect body weight and food intake. Free fatty acid receptor 2 (Ffar2), a G-protein coupled receptor recognizing SCFAs and stimulating GLP-1 production, was decreased in colon. The colonic Hydroxycarboxylic acid receptor 2 (Hcar2) and Tight junction protein-1 (Tjp1) marginally increased but expression of inflammatory cytokines was not altered, implicating that anti-obesity effects of butyrate were not primarily through colon. In the liver, butyrate showed significantly decreased Ffar2 and Peroxisome proliferator–activated receptor-γ (Ppar-γ). In the butyrate group, aberrant phenotypes were observed including hyperlipidemia and alteration of serum level of adiponectin without change in fecal energy density. Intriguingly, in the 3T3-L1 cell line, fat accumulation was significantly stimulated at lower concentration of butyrate with elevated expression of Ffar2 and Ppar-γ. High concentration of butyrate reduced Ffar2 and Ppar-γ and suppressed adipocytic fat accumulation. Conclusions Our results suggested that dietary butyrate prevented diet-induced obesity despite increased food intake. Moreover, butyrate may regulate lipid metabolism in a dose-dependent manner. Funding Sources This research was supported by Basic Science Research Program through the NRF funded by the Ministry of Education. J.S is grateful for financial support from Hyundai Motor Chung Mong-Koo Foundation.