The regulatory role of eosinophils in adipose tissue depends on autophagy

Abstract

IntroductionObesity is a metabolic condition that elevates the risk of all-cause mortality. Brown and beige adipose tissues, known for their thermogenic properties, offer potential therapeutic targets for combating obesity. Recent reports highlight the role of immune cells, including eosinophils, in adipose tissue homeostasis, while the underlying mechanisms are poorly understood.MethodsTo study the role of autophagy in eosinophils in this process, we used a genetic mouse model lacking autophagy-associated protein 5 (Atg5), specifically within the eosinophil lineage (Atg5eoΔ).ResultsThe absence of Atg5 in eosinophils led to increased body weight, impaired glucose metabolism, and alterations in the cellular architecture of adipose tissue. Our findings indicate that Atg5 modulates the functional activity of eosinophils within adipose tissue rather than their abundance. Moreover, RNA-seq analysis revealed upregulation of arginase 2 (Arg2) in Atg5-knockout eosinophils. Increased Arg2 activity was shown to suppress adipocyte beiging. Furthermore, we observed enrichment of the purine pathway in the absence of Atg5 in eosinophils, leading to a pro-inflammatory shift in macrophages and a further reduction in beiging.DiscussionThe data shed light on the importance of autophagy in eosinophils and its impact on adipose tissue homeostasis by suppressing Arg2 expression and limiting inflammation in adipose tissue.

Autophagy and inflammation an intricate affair in the management of obesity and metabolic disorders: evidence for novel pharmacological strategies?

“…In this regard, Jansen et al (2012) have demonstrated that the inhibition of autophagy increases the gene expression and secretion of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8 in the adipocytes of obese people and in the adipose tissue of obese mice, thus suggesting that autophagy may dampen excessive inflammation in adipose tissue during obesity. Moreover, in a very recent study ( Hosseini et al, 2024 ) the authors investigated the role of autophagy in eosinophils, immune cells strongly involved in adipose tissue homeostasis. They used a genetic mouse model lacking Atg5 specifically within the eosinophils and they observed that the absence of Atg5 was associated with an increase in body weight and alterations of the adipose tissue cellular architecture.…”