Related Experiment Video
Updated: Dec 13, 2025
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
CTRP12 inhibits triglyceride synthesis and export in hepatocytes by suppressing HNF-4α and DGAT2 expression
Stefanie Y Tan1,2, Hannah C Little1, Dylan C Sarver1
1Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract:
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.
Insights
C1q/TNF-related protein 12 (CTRP12) regulates lipid metabolism by inhibiting triglyceride synthesis and secretion in liver cells. This adipokine
Area of Science:
- Metabolic regulation by adipokines
- Cellular lipid metabolism
- Hepatocyte function
Background:
- C1q/TNF-related protein 12 (CTRP12) is an adipokine with reduced levels in obesity and diabetes.
- Previous studies suggest CTRP12 influences lipid metabolism and adiposity, but its cellular effects are unclear.
Purpose of the Study:
- To investigate the direct role of CTRP12 in regulating lipid synthesis and secretion in hepatocytes.
- To elucidate the molecular mechanisms by which CTRP12 affects cellular lipid metabolism.
Main Methods:
- In vitro studies using hepatoma cells and primary mouse hepatocytes treated with CTRP12.
- Analysis of gene expression for key enzymes in triglyceride synthesis (GPAT, DGAT) and VLDL export (HNF-4α, MTTP).
- In vivo studies involving CTRP12 overexpression in mice to assess serum triglyceride levels.
Main Results:
- CTRP12 treatment inhibited triglyceride synthesis by suppressing GPAT and DGAT expression in hepatocytes.
- CTRP12 downregulated HNF-4α and MTTP, reducing very-low-density lipoprotein (VLDL)-triglyceride export.
- Overexpression of CTRP12 in mice led to lower fasting and postprandial serum triglyceride levels.
Conclusions:
- CTRP12 directly regulates lipid synthesis and secretion in hepatocytes.
- CTRP12 plays a significant role in maintaining lipid homeostasis within the liver.
- CTRP12 represents a potential therapeutic target for metabolic disorders characterized by dyslipidemia.
