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

iScience

Aakash Y. Gandhi¹  Arun Gupta¹  Rodney E. Infante²  Tong Guo³  Puneeth Iyengar³  Jorge Z. Granados³  Bret M. Evers³  Jinhai Yu⁴ 

[1] Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA;Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA;Center for Human Nutrition, University of Texas Southwestern Medical Center, 5300 Harry Hines Boulevard, Dallas, TX, USA;Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA;

关键词: Biological Sciences;    Animal Physiology;    Cellular Physiology;    Endocrinology;    Cell Biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown