The present review focuses on the roles and underlying mechanisms of action of hepatic 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-1α and HNF-1β isomers can form heterodimers. Both homo- and heterodimers recognize and bind to specific

cis

-acting elements in gene promoters to transactivate transcription and to coordinate 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-related genes

such as

peroxisome proliferator-activated receptor γ (PPARγ)

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 hepatocellular 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 summary

HNF-1 transcriptionally regulates lipid-related genes to manipulate intracorporeal balance of lipid metabolism and to suppress the development of lipid metabolism disorders.