Abstract
Alcohol-associated liver disease (ALD) is one of the major chronic liver diseases and despite the dire clinical needs and extensive research efforts, no effective therapies are available for late-stages of ALD except for liver transplantation. Adipose tissue dysfunction has been implicated in the progression of ALD. Furthermore, it has been previously suggested that thermogenic fat can be activated after alcohol consumption. In this study, increased thermogenic gene expression was detected in both classical brown adipose tissue and beige adipocytes in mice that were given alcohol challenges even when housed at thermoneutrality. In particular, higher expression level of Prdm16, the key transcriptional co-component for beige fat function, was observed in the subcutaneous fat of mice after alcohol challenges. The objective of the present study is to explore the functional significance of adipocyte PRDM16 in the context of ALD. Even though Prdm16 adipocyte-specific-deleted mice (Prdm16-adKO) did not show liver defects at the basal level, following two different alcohol challenge regimens, exacerbated ALD phenotypes were observed in Prdm16-adKO mice compared to that of the control Prdm16 fl/fl mice. Mechanistic investigation suggests that adipose dysfunction after alcohol abuse, including alcohol-induced changes in adipose lipolytic activity, fatty acid oxidation and adipokine levels, may render the worsened ALD phenotype in Prdm16-adKO mice. These results indicate PRDM16-mediated signaling in fat plays a protective role against liver injury caused by alcohol abuse, suggesting it may represent a potential therapeutic target against ALD.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.