The direct and indirect inhibition of proinflammatory adipose tissue macrophages by acarbose in diet-induced obesity

Abstract

Inflammation is critical for obesity and obesity-induced insulin resistance (IR). In this study, we reveal the function and mechanism of acarbose on adipose tissue macrophage (ATM)-mediated inflammation in obesity and obesity-induced IR. First, acarbose enhances the abundance of propionic acid-producing Parasutterella , therefore indirectly inhibiting the survival and proinflammatory function of M1-like ATMs via GPR43. Most interestingly, acarbose can directly inhibit M1-like ATM-mediated inflammation through GPR120. Diet-induced obese mice exhibit nitrobenzoxadiazoles (NBD) fluorescence-labeled ATMs, but lean mice that also orally received NBD fluorescence-labeled acarbose do not exhibit NBD fluorescence-labeled ATMs. This direct inhibition of macrophages by acarbose is validated in mouse and human macrophages in vitro . In conclusion, our study reveals that acarbose directly and indirectly inhibits proinflammatory macrophage phenotype, which contributes to the improvement of obesity and obesity-induced IR. The understanding of the immune regulatory effects of acarbose may extend its potential for further therapeutic applications. • Acarbose increases propionic acid-producing gut Parasutterella in obese mice • Propionic acid inhibits M1-like adipose tissue macrophage via GPR43 • Parasutterella administration reduces obesity and adipose inflammation in mice • Acarbose directly inhibits M1-like macrophage proinflammation through GPR120 Li et al. identify that acarbose enhances the abundance of propionic acid-producing Parasutterella , therefore indirectly inhibiting M1-like adipose tissue macrophages (ATMs) via GPR43 in diet-induced obese mice. Meanwhile, acarbose directly inhibits M1-like ATM proinflammation through GPR120, thus leading to a reduction in adipose tissue inflammation overall.