肝巨噬细胞中生长激素作用的消除导致肝脏CD36表达增加和非酒精性脂肪性肝病加重。
Abrogation of GH action in Kupffer cells results in increased hepatic CD36 expression and exaggerated nonalcoholic fatty liver disease.
作者信息
Zhang Sherry, Lu Chunxia, Das Arun K, Pasupulati Anil K, Menon Ram K
机构信息
Departments of Pediatrics & Communicable Diseases, University of Michigan, United States.
Department of Internal Medicine, University of Michigan, United States.
出版信息
Growth Horm IGF Res. 2018 Oct-Dec;42-43:74-79. doi: 10.1016/j.ghir.2018.10.001. Epub 2018 Oct 4.
OBJECTIVE
To investigate the effects of GH signaling on Kupffer cells and the resulting changes in lipid homeostasis and their underlying mechanism(s) in the livers of diet-induced obese (DIO) mice.
DESIGN
Male macrophage specific-growth hormone receptor knockout mice (MacGHR KO) and their litter mate controls were fed a high fat diet containing 60% calories from fat for 26 weeks. Lipid content and lipid profiles in the liver and circulation were analyzed. Expression levels of CD36 in the liver were quantified by RT-PCR and Western Blot.
RESULTS
Increased hepatic lipid content and abundance of long-chain unsaturated fatty acids were observed in the liver of MacGHR KO mice. These findings were associated with increased steady state levels of CD36 mRNA and protein in MacGHR KO mice when compared with their litter mate controls.
CONCLUSION
GH action in Kupffer cells is required for maintaining hepatic lipid homeostasis, in part via regulation of hepatic CD36 expression.
目的
研究生长激素（GH）信号传导对库普弗细胞的影响，以及饮食诱导肥胖（DIO）小鼠肝脏中脂质稳态的变化及其潜在机制。
设计
雄性巨噬细胞特异性生长激素受体敲除小鼠（MacGHR KO）及其同窝对照小鼠喂食含60%热量来自脂肪的高脂肪饮食26周。分析肝脏和循环中的脂质含量及脂质谱。通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法（Western Blot）对肝脏中CD36的表达水平进行定量。
结果
与同窝对照小鼠相比，MacGHR KO小鼠肝脏中观察到肝脂质含量增加以及长链不饱和脂肪酸丰度增加。这些发现与MacGHR KO小鼠中CD36 mRNA和蛋白质的稳态水平升高有关。
结论
库普弗细胞中的GH作用对于维持肝脏脂质稳态是必需的，部分是通过调节肝脏CD36表达来实现。
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