“Spexin improves adipose tissue inflammation and macrophage recruitment in obese mice”

Abstract

Spexin (SPX) is a novel adipokine related to many metabolic effects, such as gastrointestinal movements, insulinand glucose homeostasis, lipid metabolism and energy balance. This study evaluates the role of SPX in theimprovement of the metabolic and inflammatory profle in fructose-rich-diet obese mice. Adult Swiss mice weresupplemented or not with fructose (20% in tap water, FRD and CTR, respectively) for 10 weeks. The last tendays, mice were treated or not with SPX (ip. 29 μg/Kg/day, FRD-SPX and CTR-SPX, respectively). A positivecorrelation was observed between body weight prior to treatment and weight loss after SPX challenge. Moreover,plasma and liver triglycerides and adipose tissue (AT) features (mass, adipocyte hypertrophy, mRNA of leptin)were improved. SPX also induced a reduction in epididymal AT (EAT) expression of TNFα, IL1β and IL6 and animprovement in IL10 and CD206. M1 macrophages in EAT, principally the Ly6C− populations (M1a and M1b),were decreased. Adipocytes from FRD-SPX mice induced less macrophage activation (IL6, mRNA and secretion)than FRD after overnight co-culture with the monocyte cell line (RAW264.7) in stimulated conditions (M1activation, LPS 100 ng/mL). Finally, in vitro, monocytes pre-incubated with SPX and stimulated with LPS showeddecreased inflammatory mRNA markers compared to monocytes with LPS alone. In conclusion, SPX decreasedbody weight and improved the metabolic profle and adipocyte hypertrophy. Inflammatory Ly6C− macrophagesdecreased, together with inflammatory marker expression. In vitro studies demonstrate that SPX induced a decrease in M1 macrophage polarization directly or through mature adipocytes.