Department of Pharmacology, Second Military Medical University / Naval Medical University, Shanghai, 200433, China.
CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Acta Pharmacol Sin. 2020 Dec;41(12):1568-1575. doi: 10.1038/s41401-020-0368-8. Epub 2020 Apr 7.
Dyslipidemia is a risk factor for cardiovascular diseases and type 2 diabetes. Several adipokines play important roles in modulation of blood lipids. Metrnl is a recently identified adipokine, and adipose Metrnl participates in regulation of blood triglyceride (TG). In this study, we generated Metrnl global, intestine-specific and liver-specific knockout mice, and explored the effects of Metrnl on serum lipid parameters. Global knockout of Metrnl had no effects on serum lipid parameters under normal chow diet, but increased blood TG by 14%, and decreased total cholesterol (TC) by 16% and high density lipoprotein cholesterol (HDL-C) by 24% under high fat diet. Nevertheless, intestine-specific knockout of Metrnl did not alter the serum lipids parameters under normal chow diet or high fat diet. Notably, liver-specific knockout of Metrnl decreased HDL-C by 24%, TC by 20% and low density lipoprotein cholesterol (LDL-C) by 16% without alterations of blood TG and nonesterified fatty acids (NEFA) under high fat diet. But deficiency of Metrnl in liver did not change VLDL secretion and expression of lipid synthetic and metabolic genes. We conclude that tissue-specific Metrnl controls different components of blood lipids. In addition to modulation of blood TG by adipose Metrnl, blood HDL-C is regulated by liver Metrnl.
血脂异常是心血管疾病和 2 型糖尿病的危险因素。几种脂肪因子在调节血脂方面发挥着重要作用。Metrnl 是一种新发现的脂肪因子，脂肪组织 Metrnl 参与调节血液甘油三酯 (TG)。在这项研究中，我们生成了 Metrnl 全局、肠道特异性和肝脏特异性敲除小鼠，并探讨了 Metrnl 对血清脂质参数的影响。Metrnl 全局敲除在正常饮食下对血清脂质参数没有影响，但在高脂肪饮食下，血液 TG 增加 14%，总胆固醇 (TC) 降低 16%，高密度脂蛋白胆固醇 (HDL-C) 降低 24%。然而，肠道特异性敲除 Metrnl 在正常饮食或高脂肪饮食下均未改变血清脂质参数。值得注意的是，肝脏特异性敲除 Metrnl 使 HDL-C 降低 24%，TC 降低 20%，LDL-C 降低 16%，而高脂肪饮食下血液 TG 和非酯化脂肪酸 (NEFA) 没有改变。但肝脏中 Metrnl 的缺乏并未改变 VLDL 的分泌和脂质合成及代谢基因的表达。我们的结论是，组织特异性 Metrnl 控制着不同的血液脂质成分。除了脂肪组织 Metrnl 对血液 TG 的调节外，肝脏 Metrnl 还调节血液 HDL-C。
