Adipocyte fatty acid binding protein deficiency protects against high fat high cholesterol diet-induced steatohepatitis in mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 708-722-Obesity: Response to Interventions
Basic
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-716
Karen SL Lam*, Ruby LC Hoo, Ida PC Lee, Lingling Shu, Mi Zhou and Aimin Xu
University of Hong Kong, Hong Kong, Hong Kong
Introduction: Non-alcoholic fatty liver disease (NAFLD), a common obesity-related inflammatory disease, is associated with increased mortality due to cardiovascular diseases and liver cancer in patients with non-alcoholic steatohepatitis (NASH). Elevated circulating levels of adipocyte fatty acid binding protein (A-FABP), a pro-inflammatory cytokine predominantly expressed in adipocytes and macrophages, have been observed in patients with NAFLD, and distinguish NASH from simple steatosis. We have also demonstrated that pharmacological inhibition of A-FABP is beneficial in the treatment of NASH induced by high fat high cholesterol (HFHC) diet in mice.  Here we investigate, in A-FABP knock-out mice, the effect of HFHC diet induced inflammation and liver injury to further delineate the role of endogenous A-FABP in the development of NASH.

Methods & Materials: A-FABP knockout (KO) mice and their wild-type (WT) littermates were fed with either standard chow (STC) or HFHC diet. Basic parameters, glucose tolerance test, insulin tolerance test were monitored during the experimental period. Mice were sacrificed after diet induction for seven months. Plasma sera were collected for biochemical analysis. Hepatic lipid profiles were determined. Hematoxylin and eosin (H&E) staining, Sirius-red staining and Oil red O staining were performed to determine the morphology, fibrosis and lipid accumulation of the liver tissues.

Results: Hepatic expression of A-FABP was significantly elevated in HFHC diet-induced WT mice. Serum alanine transaminase level was significantly lower in the A-FABP KO mice, on HFHC diet, compared to their WT littermates, accompanied by a significant reduction in diet-induced hepatic triglyceride content. HFHC diet-induced macrophage infiltration, fibrosis and steatosis in the liver were also diminished in A-FABP KO mice. Moreover, the A-FABP KO mice displayed improved glucose tolerance and insulin sensitivity, compared to their WT littermates, despite a greater increase in body weight on HFHC diet.

Conclusion: Our data suggest that A-FABP deficiency protects against HFHC diet induced steatosis, inflammation and fibrosis in the liver, in keeping with a significant role of A-FABP in the development of NASH.

Nothing to Disclose: KSL, RLH, IPL, LS, MZ, AX

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This study was supported by RGC HKU 768209M.