| First Author | Guo T | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 3 | Pages | 102227 |
| PubMed ID | 33748712 | Mgi Jnum | J:336932 |
| Mgi Id | MGI:6717615 | Doi | 10.1016/j.isci.2021.102227 |
| Citation | Guo T, et al. (2021) LIFR-alpha-dependent adipocyte signaling in obesity limits adipose expansion contributing to fatty liver disease. iScience 24(3):102227 |
| abstractText | 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-alpha)-dependent cytokine signaling in DIO, we created an adipocyte-specific LIFR knockout mouse model (Adipoq-Cre;LIFR (fl/fl) ). Differentiated adipocytes derived from this model blocked LIF-induced triacylglycerol lipolysis. Adipoq-Cre;LIFR (fl/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-alpha signals adipocytes through STAT3, we also created an Adipoq-Cre;STAT3 (fl/fl) model that showed similar findings when fed a HFD as Adipoq-Cre;LIFR (fl/fl) mice. These findings establish the importance of obesity-associated LIFR-alpha/JAK/STAT3 inflammatory signaling in adipocytes, blocking further adipose expansion in DIO contributing to ectopic liver triacylglyceride accumulation. |
