Adipocyte autophagy-mediated signals in the control of macrophage phenotype during diet-induced obesity

A hallmark of obesity is a pathological expansion of white adipose tissue (WAT), accompanied by marked tissue dysfunction and fibrosis. Autophagy promotes adipocyte differentiation and lipid homeostasis, but its role in obese adipocytes and adipose tissue dysfunction remains incompletely understood. Using a mouse model, we demonstrate that autophagy is a key tissue-specific regulator of WAT remodelling in diet-induced obesity. Importantly, loss of adipocyte autophagy substantially exacerbates pericellular fibrosis in visceral WAT. Change in WAT architecture correlates with increased infiltration of macrophages with tissue-reparative, fibrotic features. To investigate the role of adipocyte autophagy in diet-induced obesity, we used Adipoq-Cre ERT2 Atg7fl/fl mice, where autophagy was inducibly depleted with administration of tamoxifen specifically in adipocytes, followed by 16 weeks of high fat diet feeding with a 60kcal% fat diet. Gonadal white adipose tissue was isolated from these mice, mechanically and enzymatically digested and macrophages were isolated using flow-assisted cell sorting (CD11b+ F4/80+ CD64+ markers). We then performed gene expression profiling analysis using data obtained from RNA-seq of macrophages isolated from either WT or adipocyte autophagy KO white adipose tissue.