Over 65 % of people with obesity display the metabolic-associated fatty liver disease (MAFLD), which can manifest as steatohepatitis, fibrosis, cirrhosis, or liver cancer. The development and progression of MAFLD involve hepatic insulin resistance and reduced insulin clearance. This review discusses the relationships between altered insulin signaling, hepatic insulin resistance, and reduced insulin clearance in the development of MAFLD and how this provides the impetus for exploring the use of insulin sensitizers to curb this disease. The review also explores the role of the insulin receptor in hepatocytes and hepatic stellate cells and how it signals in metabolic and end-stage liver diseases. Finally, we discuss new research findings that indicate that advanced hepatic diseases may be an insulin-sensitive state in the liver and deliberate whether insulin sensitizers should be used to manage late-stage liver diseases.
|Journal||Metabolism: Clinical and Experimental|
|State||Published - Aug 2023|
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health grant R01DK121797 (T.D.H.J.), and R01DK054254 , R01DK124126 , and R01DK129877 (S.M.N.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- Fatty liver
- Hepatic stellate cells
- Insulin clearance
- Insulin resistance
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism