Adipocyte Inflammation Is Essential for Healthy Adipose Tissue Expansion and Remodeling

Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin. [Display omitted] •Adipocyte inflammation facilitates adipose tissue expansion and remodeling•Suppressed adipocyte inflammation leads to adipose tissue dysfunction•Suppressed adipocyte inflammation leads to systemic metabolic disturbances•Mesenteric adipose tissue is important for proper intestinal barrier function Contrary to the idea that inflammation plays a negative role in metabolism, Wernstedt Asterholm and colleagues show that proinflammatory signals in the adipocyte are required for proper adipose tissue remodeling and expansion. Adipose tissue inflammation plays an adaptive response for adipocyte expansion and proper intestinal barrier function.