Adipocyte autophagy limits gut inflammation by controlling oxylipin levels

Abstract

Autophagy is a critical cellular recycling pathway which is genetically linked to the development of intestinal inflammation in humans. Inflammation drives adipose tissue breakdown and provision of major nutrients such as free fatty acids (FFA). However, the effect of autophagy-mediated FFA release by adipocytes in immune-mediated inflammatory diseases remains unexplored. In a mouse model of intestinal inflammation, we found that visceral adipocytes upregulate autophagy at peak inflammation. Adipocyte-specific loss of the key autophagy gene Atg7 (Atg7Ad) resulted in the exacerbation of intestinal inflammation. TNFα-induced lipolysis was impaired in Atg7-deficient adipocytes leading to the reduced availability of several FFA species, and decreased expression of the FFA transporter CD36 on adipose tissue macrophages (ATMs). Visceral adipose tissues from Atg7Ad mice released less IL-10 resulting in lower levels of circulating IL-10 in colitis. ATMs present the main source of adipose tissue-derived IL-10 during colitis. In vitro assays confirmed that FFA restriction from macrophages reduced CD36 expression and diminished IL-10 production. Taken together, our study demonstrates that autophagy-mediated FFA release from adipocytes directs anti-inflammatory responses in ATMs, which in turn conveys protective effects for distant intestinal inflammation.

Hub gene mining and immune microenvironment analysis of autophagy in rheumatoid arthritis

“…Autophagy is a common metabolic process in eukaryotes that maintains homeostasis in the intracellular environment, and as an important self-protection mechanism, autophagy participates in various metabolic processes in the body and affects the development of diseases [30] . Some studies suggest that autophagy participates in oxidative stress reactions, helping to mitigate and eliminate damage caused by oxidative stress, thereby slowing down the process of cell death [31] . Biomarkers have been considered important tools for cancer diagnosis and targeted treatment.…”