LIFR-α-dependent adipocyte signaling in obesity limits adipose expansion contributing to fatty liver disease

• Main Authors: Tong Guo, Arun Gupta, Jinhai Yu, Jorge Z. Granados, Aakash Y. Gandhi, Bret M. Evers, Puneeth Iyengar, Rodney E. Infante
• Format: Article
• Language: English
• Published: Elsevier 2021-03-01
• Series: iScience
• Subjects: Biological Sciences; Animal Physiology; Cellular Physiology; Endocrinology; Cell Biology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221001954
• ISSN: 2589-0042

Summary: The role of chronic adipose inflammation in diet-induced obesity (DIO) and its sequelae including fatty liver disease remains unclear. Leukemia inhibitory factor (LIF) induces JAK-dependent adipocyte lipolysis and altered adipo/cytokine expression, suppressing in vivo adipose expansion in normal and obese mouse models. To characterize LIF receptor (LIFR-α)-dependent cytokine signaling in DIO, we created an adipocyte-specific LIFR knockout mouse model (Adipoq-Cre;LIFRfl/fl). Differentiated adipocytes derived from this model blocked LIF-induced triacylglycerol lipolysis. Adipoq-Cre;LIFRfl/fl mice on a high-fat diet (HFD) displayed reduced adipose STAT3 activation, 50% expansion in adipose, 20% body weight increase, and a 75% reduction in total hepatic triacylglycerides compared with controls. To demonstrate that LIFR-α signals adipocytes through STAT3, we also created an Adipoq-Cre;STAT3fl/fl model that showed similar findings when fed a HFD as Adipoq-Cre;LIFRfl/fl mice. These findings establish the importance of obesity-associated LIFR-α/JAK/STAT3 inflammatory signaling in adipocytes, blocking further adipose expansion in DIO contributing to ectopic liver triacylglyceride accumulation.