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标题：LIFR-α-dependent adipocyte signaling in obesity limits adipose expansion contributing to fatty liver disease
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作者：Tong Guo ; Arun Gupta ; Jinhai Yu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：3
页码：1-27
DOI：10.1016/j.isci.2021.102227
语种：English
出版社：Elsevier
摘要：SummaryThe 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, suppressingin vivoadipose expansion in normal and obese mouse models. To characterize LIF receptor (LIFR-α)-dependent cytokine signaling in DIO, we created an adipocyte-specificLIFRknockout mouse model (Adipoq-Cre;LIFRfl/fl). Differentiated adipocytes derived from this model blocked LIF-induced triacylglycerol lipolysis.Adipoq-Cre;LIFRfl/flmice 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 anAdipoq-Cre;STAT3fl/flmodel that showed similar findings when fed a HFD asAdipoq-Cre;LIFRfl/flmice. 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.Graphical abstractDisplay OmittedHighlights•LIFR-α signaling induces adipocyte lipolysis, restricting adipose expansion in DIO•LIFR-α signaling requires STAT3 for adipocyte lipolysis•LIFR-α/JAK/STAT3 lipolysis signaling in adipocytes promotes hepatic steatosisBiological Sciences ; Animal Physiology ; Cellular Physiology ; Endocrinology ; Cell Biology