Transcriptional control by HNF-1: Emerging evidence showing its role in lipid metabolism and lipid metabolism disorders

The present review focuses on the roles and underlying mechanisms of action of he-patic nuclear factor-1 (HNF-1) in lipid metabolism and the development of lipid metabolism disorders. HNF-1 is a transcriptional regulator that can form homodimers, and the HNF-1a and HNF-1b isomers can form heterodimers. Both homo-and heterodimers recognize and bind to specific cis-acting elements in gene promoters to transactivate transcription and to coordi-nate the expression of target lipid-related genes, thereby influencing the homeostasis of lipid metabolism. HNF-1 was shown to restrain lipid anabolism, including synthesis, absorption, and storage, by inhibiting the expression of lipogenesis-r elated genes, such as peroxisome proliferator-activated receptor g (PPARg) and sterol regulatory element-binding protein-1/ 2 (SREBP-1/2). Moreover, HNF-1 enhances the expression of various genes, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), glutathione peroxidase 1 (GPx1), and suppressor of cytokine signaling-3 (SOCS-3) and negatively regulates signal transducer and activator of transcription (STAT) to facilitate lipid catabolism in hepatocytes. HNF-1 reduces hepatocellu-lar lipid decomposition, which alleviates the progression of nonalcoholic fatty liver disease (NAFLD). HNF-1 impairs preadipocyte differentiation to reduce the number of adipocytes, stunting the development of obesity. Furthermore, HNF-1 reduces free cholesterol levels in the plasma to inhibit aortic lipid deposition and lipid plaque formation, relieving dyslipidemia and preventing the development of atherosclerotic cardiovascular disease (ASCVD). In sum-mary, HNF-1 transcriptionally regulates lipid-related genes to manipulate intracorporeal bal-ance of lipid metabolism and to suppress the development of lipid metabolism disorders. Copyright (c) 2021, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).