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SerpinA3N deficiency attenuates steatosis and enhances insulin signaling in male mice
- Source :
- J Endocrinol
- Publication Year :
- 2023
-
Abstract
- Aberrant hepatic lipid metabolism is the major cause of non-alcoholic fatty liver disease (NAFLD) and is associated with insulin resistance and type 2 diabetes. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N) is highly expressed in the liver, however its functional role in regulating NAFLD and associated metabolic disorders are not known. Male wildtype (WT) and hepatocyte Serpina3N knockout (HKO) mice were fed a control diet (CD), methionine and choline deficient (MCD) diet or high fat high sucrose (HFHS) diet to induce NAFLD and markers of lipid metabolism and glucose homeostasis were assessed. SerpinA3N protein was markedly induced in mice with fatty livers. Hepatic deletion of SerpinA3N attenuated steatosis which correlated with altered lipid metabolism genes, increased fatty acid oxidation activity and enhanced insulin signaling in mice with NAFLD. Additionally, SerpinA3N HKO mice had reduced epididymal white adipose tissue (eWAT) mass, leptin and insulin levels, improved glucose tolerance and enhanced insulin sensitivity which was associated with elevated insulin-like growth factor binding protein-1 (IGFBP1) and activation of the leptin receptor (LEPR)-STAT3 signaling pathway. Our findings provide a novel insight for the functional role for SerpinA3N in regulating NAFLD and glucose homeostasis.
- Subjects :
- Endocrinology
Endocrinology, Diabetes and Metabolism
Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Endocrinol
- Accession number :
- edsair.doi.dedup.....ac1a8346abc971e54bc8b10ffe4cfb18