Hepatic RACK1 deletion disturbs lipid and glucose homeostasis independently of insulin resistance

doi:10.1530/JOE-22-0076

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	Hepatic RACK1 deletion disturbs lipid and glucose homeostasis independently of insulin resistance
	Qin, Wanying; Zhang, Ting; Ge, Mingxia; Zhou, Huimin; Xu, Yuhui; Mu, Rongfang; Huang, Chaoguang; Liu, Daowei; Huang, Bangrui; Wang, Qian; Kong, Qinghua; Kong, Qingpeng; Li, Fei; Xiong, Wenyong
	2022
发表期刊	JOURNAL OF ENDOCRINOLOGY
卷号	254 期号:3 页码:151-165
摘要	Receptor for activated C kinase 1 (RACK1) is a versatile protein involved in multiple biological processes. In a previous study by Zhao et al., hepatic RACK1 deletion in mice led to an inhibition of autophagy, blocked autophagy-dependent lipolysis, and caused steatosis. Using the same mouse model (RACK1(hep-/-)), we revealed new roles of RACK1 in maintaining bile acid homeostasis and hepatic glucose uptake, which further affected circulatory lipid and glucose levels. To be specific, even under hepatic steatosis, the plasma lipids were generally reduced in RACK1(hep-/-) mouse, which was due to the suppression of intestinal lipid absorption. Accordingly, a decrease in total bile acid level was found in RACK1(hep-/-) livers, gallbladders, and small intestine tissues, and specific decrease of 12-hydroxylated bile acids was detected by liquid chromatography-mass spectrometry. Consistently, reduced expression of CYP8B1 was found. A decrease in hepatic glycogen storage was also observed, which might be due to the inhibited glucose uptake by GLUT2 insufficiency. Interestingly, RACK1-KO-inducing hepatic steatosis did not raise insulin resistance (IR) nor IR-inducing factors like endoplasmic reticulum stress and inflammation. In summary, this study uncovers that hepatic RACK1 might be required in maintaining bile acid homeostasis and glucose uptake in hepatocytes. This study also provides an additional case of hepatic steatosis disassociation with insulin resistance.
关键词	RACK1 bile acid glucose metabolism insulin sensitivity ENDOPLASMIC-RETICULUM STRESS C-KINASE 1 HEPATOCELLULAR-CARCINOMA STEROL 12-ALPHA-HYDROXYLASE DOWN-REGULATION ER STRESS KAPPA-B RECEPTOR ACTIVATION GROWTH
DOI	10.1530/JOE-22-0076
收录类别	SCI
WOS记录号	WOS:000848359900002
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74773
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Qin, Wanying,Zhang, Ting,Ge, Mingxia,et al. Hepatic RACK1 deletion disturbs lipid and glucose homeostasis independently of insulin resistance[J]. JOURNAL OF ENDOCRINOLOGY,2022,254(3):151-165.
APA	Qin, Wanying.,Zhang, Ting.,Ge, Mingxia.,Zhou, Huimin.,Xu, Yuhui.,...&Xiong, Wenyong.(2022).Hepatic RACK1 deletion disturbs lipid and glucose homeostasis independently of insulin resistance.JOURNAL OF ENDOCRINOLOGY,254(3),151-165.
MLA	Qin, Wanying,et al."Hepatic RACK1 deletion disturbs lipid and glucose homeostasis independently of insulin resistance".JOURNAL OF ENDOCRINOLOGY 254.3(2022):151-165.

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