CONICET | Buscador de Institutos y Recursos Humanos

Spexin (SPX) is a new adipokine involved in many processes, such as energy balance, lipid metabolism, glucose homeostasis and weight control. SPX plasma levels were decreased in obesity/metabolic syndrome (MS) cohorts. Therefore, the hallmarks of obesity and MS are low chronic inflammation and adipocyte hypertrophy. Thus, the aim of this work was to evaluate SPX as able to modulate the innate immune system in obese mice. Swiss mice were supplemented with a fructose rich diet (FRD, 20%w/v) or tap water for 10weeks. Ten days prior to the end of protocol, mice were randomly divided and intraperitoneally injected with SPX 29μg/kg (C-SPX and F-SPX) or PBS (CTR and FRD). Caloric intake and body weight were recorded. At the end of protocol, plasma samples were collected and epididymal adipose tissue (EAT) was dissected, weighted and processed for qPCR and flow cytometry analysis. We found a significant negative correlation between body weight and body weight variation during SPX treatment in F-SPX and C-SPX. Glycaemia was unchanged, but plasma triglycerides were decreased only in F-SPX vs. FRD mice and were similar to CTR/C-SPX levels. F-SPX also had significantly less EAT mass, reaching values similar to CTR/C-SPX. mRNA expression of pro-inflammatory markers in EAT decreased in both groups treated with SPX vs. their counterparts. IL10, an anti-inflammatory marker, increased in F-SPX mice reaching similar values to CTR/C-SPX. Flow cytometry of stromal vascular fraction from EAT showed that ly6C+ monocytes and M1 macrophages were significantly decreased in SPX treated animals vs. their counterparts. M2 macrophages were increased in F-SPX, restoring the population to normal values. In conclusion, SPX induced a decrease in the inflammatory markers and restored the anti-inflammatory profile in EAT upon FRD. Furthermore, the negative correlation between body weight and weight variation indicates a possible use of SPX as a therapy for obesity/MS. PICT2015-2352.