mTORC1 inhibition uncouples lipolysis and thermogenesis in white adipose tissue to contribute to alcoholic liver disease

Bibliographic Details
Title: mTORC1 inhibition uncouples lipolysis and thermogenesis in white adipose tissue to contribute to alcoholic liver disease
Authors: Qing Song, Yingli Chen, Qinchao Ding, Alexandra Griffiths, Lifeng Liu, Jooman Park, Chong Wee Liew, Natalia Nieto, Songtao Li, Xiaobing Dou, Yuwei Jiang, Zhenyuan Song
Source: Hepatology Communications, Vol 7, Iss 3, Pp e0059-e0059 (2023)
Publisher Information: Wolters Kluwer Health/LWW, 2023.
Publication Year: 2023
Collection: LCC:Diseases of the digestive system. Gastroenterology
Subject Terms: Diseases of the digestive system. Gastroenterology, RC799-869
More Details: Background:. Adipose tissue thermogenic activities use fatty acids from lipolysis for heat generation. Therefore, a tight coupling between lipolysis and thermogenesis is physiologically imperative in maintaining not only body temperature but also lipids homeostasis. Adipose tissue dysfunction contributes to alcoholic liver disease (ALD). Here, studies were conducted to examine how alcohol intake affects adipose tissue thermogenic activities and whether altered adipose tissue thermogenesis contributes to ALD. Methods:. Both the Lieber-DeCarli and the NIAAA mouse models of ALD were used. Denervation surgery in epididymal fat pads was performed. CL316,243, a selective β3-adrenoceptor agonist, SR59230A, a selective β3 adrenoceptor (ADRB3) antagonist, and rapamycin, a selective mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, were administrated through i.p. injection. Adipocyte-specific Prdm16 knockout mice were subjected to alcohol-containing diet chronically. Results:. Chronic alcohol consumption, which enhances adipose tissue lipolysis, inhibits thermogenic activities of beige adipocytes in inguinal white adipose tissue (WAT), leading to an uncoupling status between lipolysis and thermogenesis in WAT at both basal and ADRB3 stimulation states. CL316,243 administration exacerbates liver pathologies of ALD. Alcohol intake inhibits mTORC1 activities in WAT. In mice, mTORC1 inhibition by rapamycin inhibits the thermogenesis of iWAT, whereas enhancing WAT lipolysis. Further investigations using adipocyte-specific Prdm16 knockout mice revealed that functional deficiency of beige adipocytes aggravates liver pathologies of ALD, suggesting that the inhibitory effect of alcohol on WAT browning/thermogenesis contributes to ALD pathogenesis. Conclusion:. Chronic alcohol consumption induces an “uncoupling status” between lipolysis and browning/thermogenesis in WAT by inhibiting mTORC1 activation. Diminished WAT browning/thermogenesis, concomitant with enhanced lipolysis, contributes to ALD pathogenesis.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2471-254X
00000000
Relation: http://journals.lww.com/10.1097/HC9.0000000000000059; https://doaj.org/toc/2471-254X
DOI: 10.1097/HC9.0000000000000059
Access URL: https://doaj.org/article/9120e3e3701f4ff49a33b97a0f6a6ef8
Accession Number: edsdoj.9120e3e3701f4ff49a33b97a0f6a6ef8
Database: Directory of Open Access Journals
More Details
ISSN:2471254X
00000000
DOI:10.1097/HC9.0000000000000059
Published in:Hepatology Communications
Language:English