How infection impacts regulation of adipocyte metabolism and does IFN? directly targets adipocytes and mediates lipid metabolism in vivo following infection
Viral infection often causes us to lose fat, but how and why this happens is unclear. The immune system plays a major role in the regulation of adipose tissue biology during homeostasis and in context of metabolic disease. Here, we investigated whether immune cells also modulate adipocyte metabolism during viral infection. We find that visceral adipose tissue transiently decreases adiposity following viral infection. Upon pathogen encounter, adipose tissue upregulates surface expression of ligands for activating receptors on NK cells, which drives their secretion of IFN?. This cytokine directly stimulates adipocytes to shift their balance from lipogenesis to lipolysis, which leads to their release of lipids in circulation, most notably of free fatty acids (FFAs). The FFA oleic acid stimulates early activated B cells by promoting oxidative phosphorylation. Oleic acid promoted expression of costimulatory B7 molecules on B cells and promoted their ability to prime CD8+ T cells. Inhibiting lipid uptake by activated B cells impaired CD8+ T cell responses, causing an increase of viral replication in vivo. Our findings uncover a new mechanism of metabolic adaptation to infection and provide better understanding of the interactions between immune cells and adipose tissue in response to inflammation. Overall design: To analyze how infection impacts regulation of adipocyte metabolism and if IFN? directly targets adipocytes and mediates lipid metabolism in vivo following infection we performed transcriptome analysis of adipose tissue from infected and non-infected IfngrFlox/Flox and AdipoqCreIfngrFlox/Flox mice. Adipocytes were isolated from VAT of these mice (4 mice for 4 diffrent conditions) and RNA was isolated.