HCBP6 deficiency exacerbates glucose and lipid metabolism disorders in non-alcoholic fatty liver mice
HCBP6 deficiency exacerbates glucose and lipid metabolism disorders in non-alcoholic fatty liver mice
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HCBP6缺乏加剧非酒精性脂肪肝小鼠的葡萄糖和脂质代谢紊乱
DOI：
10.1016/j.biopha.2020.110347
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发表时间：
2020-09-01
影响因子：
7.5
通讯作者：
Cheng, Jun
中科院分区：
文献类型：
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作者：
Lu, Hongping;Yuan, Xiaoxue;Cheng, Jun
背景资料：非酒精性脂肪性肝病（nonalcoholic fatty liver disease，NAFLD）常伴有肥胖、糖尿病、血脂异常等代谢综合征，已成为全球性的健康问题。我们的前期研究表明，HCV核心蛋白结合蛋白6（HCBP 6）可以维持肝细胞甘油三酯的稳态。然而，HCBP6在NAFLD及其相关代谢紊乱中的作用仍不完全清楚。方法：采用qRT-PCR、Western blot和免疫组化方法检测肝脏HCBP6的表达。构建HCBP6敲除（HCBP6-KO）小鼠并喂食高脂饮食（HFD）以诱导NAFLD。通过HE染色、qRT-PCR、Western blot和GTT检测HCBP6对糖脂代谢的影响。结果：HFD组小鼠HCBP 6表达降低，HFD组小鼠HCBP 6表达降低。HCBP6缺乏可使HFD诱导的NAFLD小鼠模型体重增加，脂肪肝加重，脂质稳态和葡萄糖稳态恶化。此外，HCBP6-KO小鼠在冷攻击后不能维持体温。HCBP6在体内可通过激活AMKP调节脂肪分解和脂肪酸氧化。此外，HCBP6的表达上调，由人参皂苷Rh2。因此，人参皂苷Rh2管理改善HFD诱导的脂肪肝和葡萄糖tolerance.Conclusions：这些研究结果表明，HCBP 6是必不可少的，在维持脂质和葡萄糖的稳态和体温。HCBP6增强的皂苷Rh2可能是一种有前途的治疗策略，用于治疗NAFLD小鼠的代谢紊乱。
Background: Non-alcoholic fatty liver disease (NAFLD), which often accompanied by metabolic syndrome, such as obesity, diabetes and dyslipidemia, has become a global health problem. Our previous results show that HCV core protein binding protein 6 (HCBP6) could maintain the triglyceride homeostasis in liver cells. However, the role of HCBP6 in NAFLD and its associated metabolic disorders remains incompletely understood.Methods: Hepatic HCBP6 expression was determined by qRT-PCR, Western blot and immunohistochemistry analysis. HCBP6 knockout (HCBP6-KO) mice were constructed and fed a high-fat diet (HFD) to induce NAFLD. The effects of HCBP6 on glucose and lipid metabolism were measured by HE staining, qRT-PCR, Western blot and GTT. Wild-type and HCBP6-KO mice kept on a HFD were treated with ginsenosides Rh2, and HE staining and GTT were used to study the function of Rh2 in metabolism disorders.Results: HCBP6 is reduced in HFD-fed mice. HCBP6 deficiency increased the body weight, aggravated fatty liver and deteriorated lipid homeostasis as well as glucose homeostasis in HFD-induced mouse model of NAFLD. Moreover, HCBP6-KO mice failed to maintain body temperature upon cold challenge. Mechanistically, HCBP6 could regulate lipolysis and fatty acid oxidation via activation of AMKP in vivo. In addition, HCBP6 expression was upregulated by ginsenosides Rh2. Accordingly, ginsenosides Rh2 administrations improved HFD-induced fatty liver and glucose tolerance.Conclusions: These findings indicated that HCBP6 is essential in maintaining lipid and glucose homeostasis and body temperature. HCBP6 augmented by ginsenosides Rh2 may be a promising therapeutic strategy for the treatment of metabolic disorders in NAFLD mice.