HCBP6 Modulates Triglyceride Homeostasis in Hepatocytes Via the SREBP1c/FASN Pathway

Abstract

Hypertriglyceridemia leads to liver steatosis, cardiovascular disease, and type 2 diabetes. Although HCBP6 (hepatitis C virus core-binding protein 6) was previously shown to be an HCV (hepatitis C virus) core-binding protein, its biological function remains unclear. Here, we demonstrate that HCBP6 negatively regulates intracellular triglyceride (TG) levels in hepatocytes. We found that bidirectional manipulation of hepatocyte HCBP6 expression by knockdown or overexpression results in increased or decreased TG accumulation, respectively. In addition, HCBP6 mRNA and protein levels exhibited significant time- and dose-dependent increases in a cellular model of lipid-overload hepatic steatosis. Furthermore, TG levels are regulated by HCBP6-sterol regulatory element binding protein 1c (SREBP1c)-mediated fatty acid synthase (FASN) expression. We also demonstrate that HCBP6 mRNA and protein expression is inhibited by microRNA-122 (miR-122), and miR-122 overexpression elicited more robust translational repression of luciferase activity driven by the full 3'-UTR of HCBP6. Taken together, our results provide new evidence that miR-122-regulated HCBP6 functions as a sensor protein to maintain intrahepatocyte TG levels.

BNIP3 induction by hypoxia stimulates FASN-dependent free fatty acid production enhancing therapeutic potential of umbilical cord blood-derived human mesenchymal stem cells

“…Previous reports presented that SREBP1c expression is responsible under hypoxic condition, which is associated with de novo lipogenesis [63], [64]. Although both SREBP1a and SREBP1c are involved in lipid metabolism [65], [66], most of previous studies present a SREBP-1c as a major regulator of FASN expression [67], [68]. Those previous findings indicate that SREBP-1c is a major regulator for FASN-induced lipogenesis in UCB-hMSCs under hypoxia.…”

Chinese Herbal Medicine Formula Shenling Baizhu San Ameliorates High-Fat Diet-Induced NAFLD in Rats by Modulating Hepatic MicroRNA Expression Profiles

“…ere is some evidence that many miRNAs are key regulators of lipid metabolism and are involved in the pathogenesis of NAFLD [11]. For instance, previous studies have reported that miR-122 may regulate cholesterol and fatty acid metabolism [12,13], and miR-21 has been demonstrated to play an important role in the hepatic inflammatory response caused by steatosis [14]. In addition, several other miRNAs have been found to be closely related to NAFLD, such as miR-33a/b, miR-34a, and miR-29 [15].…”

NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis

“…The pENTER (pNC) and Penter‐NS5ABP37 (pNS5ABP37) plasmids were purchased from Vigene (ShanDong, China); siRNA targeting NS5ABP37 and a negative control siRNA were purchased from GenePharma (Jiangsu, China) (Table ). The pGL4.10 vector‐SREBP1c promoter and pGL4.10 vector‐SREBP2 were kind gifts from Dr. Lili Gao and Dr. Min Li …”