Impact of Breaking up of Sitting Time on Anti-inflammatory Response Induced by Extracellular Vesicles.

Physical inactivity and sedentary behaviors (SB) have promoted a dramatic increase in the incidence of a host of chronic disorders over the last century. The breaking up of sitting time (i.e., sitting to standing up transition) has been proposed as a promising solution in several epidemiological and clinical studies. In parallel to the large interest it initially created, there is a growing body of evidence indicating that breaking up prolonged sedentary time (i.e., > 7 h in sitting time) could reduce overall mortality risks by normalizing the inflammatory profile and cardiometabolic functions. Recent advances suggest that the latter health benefits, may be mediated through the immunomodulatory properties of extracellular vesicles. Primarily composed of miRNA, lipids, mRNA and proteins, these vesicles would influence metabolism and immune system functions by promoting M1 to M2 macrophage polarization (i.e., from a pro-inflammatory to anti-inflammatory phenotype) and improving endothelial function. The outcomes of interrupting prolonged sitting time may be attributed to molecular mechanisms induced by circulating angiogenic cells. Functionally, circulating angiogenic cells contribute to repair and remodel the vasculature. This effect is proposed to be mediated through the secretion of paracrine factors. The present review article intends to clarify the beneficial contributions of breaking up sitting time on extracellular vesicles formation and macrophage polarization (M1 and M2 phenotypes). Hence, it will highlight key mechanistic information regarding how breaking up sitting time protocols improves endothelial health by promoting antioxidant and anti-inflammatory responses in human organs and tissues.

Immunometabolic Changes in Hepatocytes Arising from Obesity and the Practice of Physical Exercise.

Over the recent years, a particular interest was shown towards understanding the roles of excessive hepatic fat accumulation and the development of obesity-related diseases. While hepatic triacylglycerol accumulation seems to be a response to the systemic increase of insulin release, fatty acid metabolites contribute to the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). It is widely accepted that NAFLD is a polygenic and multifactorial disease under the influence of critical behavioral factors such as overeating and sedentary lifestyles. The progression of the disease is proposed to include the accumulation of lipids in hepatocytes, but liver damage would be mainly initiated through an exaggerated activation of the immune system. This inflammatory response would be triggered by the increase in cytokine production followed by TLR-4 activation and NF-kB pathways. Interestingly, cytokines as IL-1ra, IL-4, IL-6 and IL-10 act as antiinflammatory in response to exercise and thus, could play an important role in the restoration of liver functions in diseased conditions. Strategies for healthy life behaviors including nutrition and regular physical exercise are recommended to counteract the dreadful effects of NAFLD. To beyond the classical effect of exercise for increasing energy expenditure and/or inducing negative energy balance, exercise also prevents and reverses the effects of disorders related to the immunometabolic profile. This suggests that exercise prescription may be an attractive alternative for the prevention of obesity and NAFLD. Thus, this review seeks to shed light on the inflammatory pathways regulating the beneficial effects of physical activity on obesity and NAFLD. We will clarify how physical activity intervenes to normalize inflammatory processes and prevent obesity and NAFLD. Finally, the exercise interventions should be individualized to facilitate behavioral and cognitive strategies in order to promote long-term adherence. A multidisciplinary approach including lifestyles, diet and exercise training interventions is considered as a "best practice" and displays the strongest liver benefits when it occurs simultaneously with weight loss.