Garlic-derived exosomes carrying miR-396e shapes macrophage metabolic reprograming to mitigate the inflammatory response in obese adipose tissue

Low-grade chronic inflammation originating from the adipose tissue and imbalance of lipid metabolism in the liver are the main drivers of the development of obesity and its related metabolic disorders. In this work, we found that garlic-derived exosomes (GDE) supplementation improved insulin resistance, altered the levels of inflammatory cytokines in serum and epididymal white adipose tissue (eWAT) by decreasing the accumulation of macrophages in HFD-fed mice. Meanwhile, we also observed that GDE regulated the expression of 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), one of the critical glycolytic enzymes, to shape the metabolic reprograming of macrophage induced by lipopolysaccharide (LPS) and mitigate the inflammatory response in adipocytes via macrophage-adipocyte cross-talk. Data from small RNA sequencing, bioinformatical analysis and the gene over-expression revealed that miR-396e, one of the most abundant miRNAs of GDE, played a critical role in promoting the metabolic reprogramming of macrophage by directly targeting PFKFB3. The findings of this study not only provide an in-depth understanding of GDE protecting against inflammation in obesity but supply evidence to study the molecular mechanisms associated with the interspecies communication.