Aerobic exercise training regulates serum extracellular vesicle miRNAs linked to obesity to promote their beneficial effects in mice.

There is a growing body of evidence that extracellular vesicles (EVs) and their cargo of RNA, DNA, and protein are released in the circulation with exercise and might mediate interorgan communication. C57BL6/J male mice were subjected to diet-induced obesity and aerobic training on a treadmill for 8 wk. The effect of aerobic training was evaluated in the liver, muscle, kidney, and white/brown adipose tissue. To provide new mechanistic insight, we profiled miRNA from serum EVs of obese and obese trained mice. We demonstrate that aerobic training changes the circulating EV miRNA profile of obese mice, including decreases in miR-122, miR-192, and miR-22 levels. Circulating miRNA levels were associated with miRNA levels in mouse liver white adipose tissue (WAT). In WAT, aerobically trained obese mice showed reduced adipocyte hypertrophy and increased the number of smaller adipocytes and the expression of Cebpa, Pparg, Fabp4 (adipogenesis markers), and ATP-citrate lyase enzyme activity. Importantly, miR-22 levels negatively correlated with the expression of adipogenesis and insulin sensitivity markers. In the liver, aerobic training reverted obesity-induced steatohepatitis, and steatosis score and Pparg expression were negatively correlated with miR-122 levels. The prometabolic effects of aerobic exercise in obesity possibly involve EV miRNAs, which might be involved in communication between liver and WAT. Our data provide significant evidence demonstrating that aerobic training exercise-induced EVs mediate the effect of exercise on adipose tissue metabolism.

Lack of adiponectin in mice accelerates high-fat diet-induced progression of chronic kidney disease.

Obesity is an independent risk factor for the development of chronic kidney disease. The pathophysiology of the obesity-induced kidney injury is complex, but evidence suggests the involvement of reduced adiponectin levels and signaling. We investigated the extent by which adiponectin contributes to the establishment and progression of renal disease in wild type (WT) and adiponectin null (adipoKO) mice fed a control or a high-fat diet (HFD) for 16 weeks. HFD induced obesity, kidney hypertrophy, albuminuria, renal lipid accumulation and decreased nephrin expression in both mice genotypes. Notably, HFD in adipoKO mice exacerbated progression of albuminuria in comparison to WT mice. In addition, lack of adiponectin per se increased kidney weight, reduced nephrin levels, up-regulated Fabp4 expression, reduced Cpt1a expression and increased miR-130 levels in kidney. Our results demonstrate that lack of adiponectin combined with a HFD contributes to accelerated kidney dysfunction.