C1q/TNF‐related protein 12 (CTRP12) is an antidiabetic adipokine whose circulating levels are reduced in obesity and diabetes. Although partial and complete loss‐of‐function mouse models suggest a role for CTRP12 in modulating lipid metabolism and adiposity, its effect on cellular lipid metabolism remains poorly defined. Here, we demonstrate a direct action of CTRP12 in regulating lipid synthesis and secretion. In hepatoma cells and primary mouse hepatocytes, CTRP12 treatment inhibits triglyceride synthesis by suppressing glycerophosphate acyltransferase (GPAT) and diacylglycerol acyltransferase (DGAT) expression. CTRP12 treatment also downregulates the expression of hepatocyte nuclear factor‐4α (HNF‐4α) and its target gene microsomal triglyceride transfer protein (MTTP), leading to reduced very‐low‐density lipoprotein (VLDL)‐triglyceride export from hepatocytes. Consistent with the in vitro findings, overexpressing CTRP12 lowers fasting and postprandial serum triglyceride levels in mice. These results underscore the important function of CTRP12 in lipid metabolism in hepatocytes.

中文翻译：

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CTRP12通过抑制HNF-4α和DGAT2表达抑制肝细胞中甘油三酯的合成和输出

C1q/TNF 相关蛋白 12 (CTRP12) 是一种抗糖尿病脂肪因子，其循环水平在肥胖和糖尿病中降低。尽管部分和完全功能丧失的小鼠模型表明 CTRP12 在调节脂质代谢和肥胖中的作用，但其对细胞脂质代谢的影响仍不清楚。在这里，我们证明了 CTRP12 在调节脂质合成和分泌方面的直接作用。在肝癌细胞和原代小鼠肝细胞中，CTRP12 处理通过抑制甘油磷酸酰基转移酶 (GPAT) 和二酰基甘油酰基转移酶 (DGAT) 的表达来抑制甘油三酯的合成。CTRP12 治疗还下调肝细胞核因子-4α (HNF-4α) 及其靶基因微粒体甘油三酯转移蛋白 (MTTP) 的表达，导致肝细胞极低密度脂蛋白 (VLDL)-甘油三酯输出减少。与体外研究结果一致，过表达 CTRP12 可降低小鼠的空腹和餐后血清甘油三酯水平。这些结果强调了 CTRP12 在肝细胞脂质代谢中的重要功能。