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There is growing body of evidence that extracellular vesicles (EVs) and their cargo of RNA, DNA, and protein are released into the circulation with exercise and might mediate inter-organ communication. C57BL6/J male mice were diet-induced obesity and subjected to aerobic training on a treadmill for 8 weeks. The effect of aerobic training was evaluated in the liver, muscle, kidney and white/brown adipose tissue. In order to provide new mechanistic insight, we profiled miRNA from serum EVs of obese and obese trained mice. We demonstrate that aerobic training changes circulating EVs 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 and 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 pro-metabolic effects of aerobic exercise in obesity possibly involves 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 effect of exercise on adipose tissue metabolism.

Parkinson's disease (PD) is associated with respiratory dysfunction. In the 6-OHDA rat model of PD this is seen as a reduction in respiratory frequency and minute ventilation during normoxia and hypercapnia stimulus. r Respiratory dysfunction is caused by neuronal death of medullary respiratory nuclei in the 6-OHDA model of PD. r Oxidative stress can be considered a strong candidate for neurodegeneration via miR-34c downregulation and pro-apoptotic signalling in respiratory neurons, preceding the functional impairment observed in the 6-OHDA model of PD.

The effect of fenofibrate on the metabolism of skeletal muscle and visceral white adipose tissue of diet-induced obese (DIO) mice was investigated. C57BL/6J male mice were fed either a control or high-fat diet for 8 weeks. Fenofibrate (50 mg/Kg BW, daily) was administered by oral gavage during the last two weeks of the experimental period. Insulin-stimulated glucose metabolism in soleus muscles, glucose tolerance test, insulin tolerance test, indirect calorimetry, lipolysis of visceral white adipose tissue, expression of miR-103-3p in adipose tissue, and miR-1a, miR-133a/b, miR-206, let7b-5p, miR-23b-3p, miR-29-3p, miR-143-3p in soleus muscle, genes related to glucose and fatty acid metabolism in adipose tissue and soleus muscle, and proteins (phospho-AMPKα2, Pgc1α, Cpt1b), intramuscular lipid staining, and activities of fatty acid oxidation enzymes in skeletal muscle were investigated. In DIO mice, fenofibrate prevented weight gain induced by HFD feeding by increasing energy expenditure; improved whole body glucose homeostasis, and in skeletal muscle, increased insulin dependent glucose uptake, miR-1a levels, reduced intramuscular lipid accumulation, and phospho-AMPKα2 levels. In visceral adipose tissue of obese mice, fenofibrate decreased basal lipolysis rate and visceral adipocytes hypertrophy, and induced the expression of Glut-4, Irs1, and Cav-1 mRNA and miR-103-3p suggesting a higher insulin sensitivity of the adipocytes. The evidence is presented herein that beneficial effects of fenofibrate on body weight, glucose homeostasis, and muscle metabolism might be related to its action in adipose tissue. Moreover, fenofibrate regulates miR-1a-3p in soleus and miR-103-3p in adipose tissue, suggesting these microRNAs might contribute to fenofibrate beneficial effects on metabolism.