Histamine regulation in glucose and lipid metabolism via histamine receptors: model for nonalcoholic steatohepatitis in mice.
Histamine regulation in glucose and lipid metabolism via histamine receptors: model for nonalcoholic steatohepatitis in mice.
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DOI：
10.2353/ajpath.2010.091198
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发表时间：
2010-08
期刊：
影响因子：
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通讯作者：
Ke-Yong Wang;A. Tanimoto;S. Yamada;Xin Guo;Yan Ding;Teruo Watanabe;Takeshi Watanabe;K. Kohno;K. Hirano;H. Tsukada;Y. Sasaguri
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文献类型：
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作者：
Ke-Yong Wang;A. Tanimoto;S. Yamada;Xin Guo;Yan Ding;Teruo Watanabe;Takeshi Watanabe;K. Kohno;K. Hirano;H. Tsukada;Y. Sasaguri
组胺被认为是能量摄入和消耗的重要调节剂。本研究的目的是评估组胺对糖脂代谢的调节以及高脂饮食引起的非酒精性脂肪性肝炎（NASH）的发生。在组胺H1（H1 R（-/-））和H2（H2 R（-/-））受体敲除小鼠和野生型小鼠中研究了组胺对葡萄糖和脂质代谢、脂肪细胞因子产生以及高脂血症诱导的肝损伤的调节。H1 R（-/-）小鼠表现出轻度增加的胰岛素抵抗。相反，H2 R（-/-）小鼠表现出严重的胰岛素抵抗和葡萄糖耐受不良。高脂肪/高胆固醇喂养增强胰岛素抵抗和葡萄糖耐受不良。用双脱氧-2-[（18）F]-氟-d-葡萄糖和正电子发射断层扫描进行的研究表明，H1 R（-/-）小鼠的脑葡萄糖分配。此外，在H2 R（-/-）小鼠中观察到严重NASH伴低脂联素血症以及肝脏甘油三酯和游离胆固醇积聚以及血肝酶增加。H1 R（-/-）小鼠表现出肥胖表型，伴有内脏脂肪过多、高瘦素血症，以及不太严重的肝脂肪变性和炎症伴肝甘油三酯升高。这些数据表明，H1 R和H2 R信号可能调节糖和脂质代谢以及高血压诱导的NASH的发展。
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.