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

TitleAdipocyte fatty acid binding protein deficiency protects against high fat high cholesterol diet-induced steatohepatitis in mice
Authors
Issue Date2013
PublisherThe Endocrine Society. The Conference program's website is located at https://endo.confex.com/endo/2013endo/webprogram/programs.html
Citation
The 95th Annual Meeting and Expo of the Endocrine Society (ENDO 2013), San Francisco, CA., 15-18 June 2013. How to Cite?
AbstractINTRODUCTION: 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.
DescriptionSession: SAT 708-722-Obesity: Response to Interventions Basic
Persistent Identifierhttp://hdl.handle.net/10722/190063

 

DC FieldValueLanguage
dc.contributor.authorLam, KSLen_US
dc.contributor.authorHoo, RLCen_US
dc.contributor.authorLee, IPCen_US
dc.contributor.authorShu, Len_US
dc.contributor.authorZhou, M-
dc.contributor.authorXu, A-
dc.date.accessioned2013-09-17T15:06:22Z-
dc.date.available2013-09-17T15:06:22Z-
dc.date.issued2013en_US
dc.identifier.citationThe 95th Annual Meeting and Expo of the Endocrine Society (ENDO 2013), San Francisco, CA., 15-18 June 2013.en_US
dc.identifier.urihttp://hdl.handle.net/10722/190063-
dc.descriptionSession: SAT 708-722-Obesity: Response to Interventions Basic-
dc.description.abstractINTRODUCTION: 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.-
dc.languageengen_US
dc.publisherThe Endocrine Society. The Conference program's website is located at https://endo.confex.com/endo/2013endo/webprogram/programs.html-
dc.relation.ispartofAnnual Meeting and Expo of the Endocrine Society, ENDO 2013en_US
dc.titleAdipocyte fatty acid binding protein deficiency protects against high fat high cholesterol diet-induced steatohepatitis in miceen_US
dc.typeConference_Paperen_US
dc.identifier.emailLam, KSL: ksllam@hku.hken_US
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hken_US
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_US
dc.identifier.authorityLam, KSL=rp00343en_US
dc.identifier.authorityHoo, RLC=rp01334en_US
dc.identifier.authorityXu, A=rp00485en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros223745en_US
dc.publisher.placeUnited States-

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