Abstract 189: Preventive effects of branched-chain amino acids supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice.

Abstract

Abstract Obesity and its associated disorders, such as non-alcoholic steatohepatitis, increase the risk of hepatocellular carcinoma (HCC). Branched-chain amino acids (BCAA), which improves protein malnutrition in patients with liver cirrhosis, reduces the risk of HCC in these patients with obesity. In the present study, the effects of BCAA supplementation on the spontaneous development of hepatic premalignant lesions, foci of cellular alteration (FCA), in db/db obese mice were examined. Male db/db mice were given a basal diet containing 3.0% of either BCAA or casein, a nitrogen content-matched control of BCAA, for 36 weeks. At sacrifice, supplementation with BCAA significantly inhibited the development of FCA when compared to casein supplementation by inhibiting cell proliferation, but inducing apoptosis. BCAA supplementation increased the expression levels of PPAR-γ, p21CIP1, and p27KIP1 mRNA and decreased the levels of c-fos and cyclin D1 mRNA in the liver. BCAA supplementation also reduced both the amount of hepatic triglyceride accumulation and the expression of IL-6, IL-1β, IL-18, and TNF-α mRNA in the liver. Increased macrophage infiltration was inhibited and the expression of IL-6, TNF-α, and MCP-1 mRNA in the white adipose tissue (WAT) were each decreased by BCAA supplementation. BCAA supplementation also reduced adipocyte size, while increasing the expression of PPAR-α, PPAR-γ, and adiponectin mRNA in the WAT compared to casein supplementation. These findings indicate that BCAA supplementation inhibits the early phase of obesity-related liver tumorigenesis by attenuating chronic inflammation in both the liver and WAT. BCAA supplementation may be useful in the chemoprevention of liver tumorigenesis in obese individuals. Citation Format: Masahito Shimizu, Daishi Terakura, Takahiro Kochi, Tomohiko Ohno, Masaya Kubota, Yohei Shirakami, Takuji Tanaka, Hisataka Moriwaki. Preventive effects of branched-chain amino acids supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 189. doi:10.1158/1538-7445.AM2013-189