Histamine Regulation in Glucose and Lipid Metabolism Via Histamine Receptors: Model for Nonalcoholic Steatohepatitis in Mice

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2010 Jun 23

PMID 20566747

Citations 25

Authors

Ke-Yong Wang

Akihide Tanimoto

Sohsuke Yamada

Xin Guo

Yan Ding

Teruo Watanabe

Takeshi Watanabe

Kimitoshi Kohno

Ken-Ichi Hirano

Hideo Tsukada

Yasuyuki Sasaguri

Affiliations

Soon will be listed here.

Abstract

Histamine has been proposed to be an important regulator of energy intake and expenditure. The aim of this study was to evaluate histamine regulation of glucose and lipid metabolism and development of nonalcoholic steatohepatitis (NASH) with a hyperlipidemic diet. Histamine regulation of glucose and lipid metabolism, adipocytokine production, and development of hyperlipidemia-induced hepatic injury were studied in histamine H1 (H1R(-/-)) and H2 (H2R(-/-)) receptor knockout and wild-type mice. H1R(-/-) mice showed mildly increased insulin resistance. In contrast, H2R(-/-) mice manifested profound insulin resistance and glucose intolerance. High-fat/high-cholesterol feeding enhanced insulin resistance and glucose intolerance. Studies with two-deoxy-2-[(18)F]-fluoro-d-glucose and positron emission tomography showed a brain glucose allocation in H1R(-/-) mice. In addition, severe NASH with hypoadiponectinemia as well as hepatic triglyceride and free cholesterol accumulation and increased blood hepatic enzymes were observed in H2R(-/-) mice. H1R(-/-) mice showed an obese phenotype with visceral adiposity, hyperleptinemia, and less severe hepatic steatosis and inflammation with increased hepatic triglyceride. These data suggest that H1R and H2R signaling may regulate glucose and lipid metabolism and development of hyperlipidemia-induced NASH.

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