Abstract
ABSTRACTChildhood obesity has reached epidemic levels, representing one of the most serious public health concerns associated with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). There is limited clinical experience concerning pediatric NAFLD patients, and thus the therapeutic options are scarce. The aim of this study was to evaluate the benefits of exercise on gut microbiota composition and functionality balance, and consequent effects on early obesity and NAFLD onset in an in vivo model. Juvenile (21-day-old) male Wistar rats fed a control diet or a high-fat diet (HFD) were subjected to a combined aerobic and resistance training protocol. Fecal microbiota was sequenced by an Illumina MiSeq system, and parameters related to metabolic syndrome, fecal metabolome, intestinal barrier integrity, bile acid metabolism and transport, and alteration of the gut-liver axis were measured. Exercise decreased HFD-induced body weight gain, metabolic syndrome and hepatic steatosis, as a result of its lipid metabolism modulatory capacity. Gut microbiota composition and functionality were substantially modified as a consequence of diet, age and exercise intervention. In addition, the training protocol increased Parabacteroides, Bacteroides and Flavobacterium genera, correlating with a beneficial metabolomic profile, whereas Blautia, Dysgonomonas and Porphyromonas showed an opposite pattern. Exercise effectively counteracted HFD-induced microbial imbalance, leading to intestinal barrier preservation, which, in turn, prevented deregulation of the gut-liver axis and improved bile acid homeostasis, determining the clinical outcomes of NAFLD. In conclusion, we provide scientific evidence highlighting the benefits of gut microbiota composition and functionality modulation by physical exercise protocols in the management of early obesity and NAFLD development.
Highlights
Childhood obesity has emerged as one of the most serious public health issues from this century, largely as a result of unhealthy dietary habits and sedentary patterns in children
Exercise attenuates high-fat diet (HFD)-induced metabolic syndrome and liver injury in our in vivo model of early obesity and non-alcoholic fatty liver disease (NAFLD) To assess the effects of exercise training on HFD-induced metabolic syndrome and obesity-related childhood NAFLD, 21-day-old Wistar rats were fed a control diet or HFD for 6 weeks and subsequently split into four subgroups, so that half of the rats from each diet group remained sedentary and the other half undertook a training protocol for an additional 5 weeks
After the first 6 weeks into the HFD-based regimen, pubertal male rats demonstrated an increase in body weight and insulin resistance [determined by the homeostatic model assessment of insulin resistance (HOMA-IR)] (Fig. S1A,B), markers of early obesity and metabolic syndrome as described for pediatric patients (Giorgio et al, 2013)
Summary
Childhood obesity has emerged as one of the most serious public health issues from this century, largely as a result of unhealthy dietary habits and sedentary patterns in children. NAFLD condition is considered the hepatic manifestation of the metabolic syndrome, associated with insulin resistance, fat infiltration in >5% of hepatocytes (steatosis), deregulated lipid metabolism, oxidative stress response and subsequent hepatotoxicity (Tiniakos et al, 2010). These hallmarks, together with gut microbiota and dysfunction of the gut-liver axis, are critical in the progression through more severe inflammatory and fibrotic stages of steatohepatitis (Tiniakos et al, 2010). Therapeutic options are scarce with respect to safety, effectiveness and patient compliance (Giorgio et al, 2013)
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