Central and peripheral effects of physical exercise without weight reduction in obese and lean mice

Abstract

To investigate the central (hypothalamic) and peripheral effects of exercise without body weight change in diet-induced obesity (DIO). Twelve-week-old male C57Bl/6 mice received a control (C) or a high-fat diet (H). Half of them had free access to running wheels for 5 days/week for 10 weeks (CE) and HE, respectively). Hypothalamic expression of genes related to energy homeostasis, and leptin (Stat3 and p-Stat3) and insulin (Akt and p-Akt) signaling were evaluated. Glucose and leptin tolerance, peripheral insulin sensitivity, and plasma insulin, leptin and adiponectin were determined. Perigonadal and retroperitoneal fat depots were increased by diet but reduced by exercise despite lack of effect of exercise on body weight. Blood glucose during intraperitoneal glucose tolerance test (ipGTT) was higher and glucose decay during intraperitoneal insulin tolerance test (ipITT) was lower in H and HE compared with C and CE. Exercise increased liver p-Akt expression and reduced fast glycemia. High-fat diet increased plasma insulin and leptin. Exercise had no effect on insulin but decreased leptin and increased adiponectin. Leptin inhibited food intake in all groups. Hypothalamic total and p-Stat3 and Akt were similar amongst the groups despite higher plasma levels of leptin and insulin in H and HE mice. High-fat diet modulated gene expression favoring a positive energy balance. Exercise only marginally changed the gene expression. Exercise induced positive changes (decreased fast glycemia and fat depots; increased liver insulin signaling and adiponectin concentration) without weight loss. Thus, despite reducing body weight could bring additional benefits, the effects of exercise must not be overlooked when weight reduction is not achieved.

Delayed Exercise Training Improves Obesity-Induced Chronic Kidney Disease by Activating AMPK Pathway in High-Fat Diet-Fed Mice

“…Interestingly, EET has been shown to present beneficial effects without weight loss, suggesting independent effects of EET on obesity-related disorders [ 37 , 38 ]. Particularly, a redistribution of body fat along with a reduced ectopic lipid accumulation and a reduction of inflammation in tissues have been revealed with exercise [ 39 ]. Despite evidence that exercise training may improve obesity-related disorders, there is still a lack of knowledge about the underlying cellular and molecular mechanisms.…”

Adiponectin—Consideration for its Role in Skeletal Muscle Health

“…Not surprisingly, because physical activity is a potent countermeasure against metabolic and CVD [93,94], studies to determine the relationship between exercise and plasma adiponectin have been plentiful. In rodents, there is evidence to suggest that moderate physical activity (10 weeks voluntary wheel or treadmill running) can increase plasma adiponectin without changes in fat mass [56,95], but this is not clear given that neither 10 weeks of endurance running at 70% maximal running capacity nor 10 weeks of high intensity interval training (HIIT) were shown to significantly increase plasma LMW and HMW adiponectin (as measured by Western Blot) in mice [96]. Similarly, systematic summaries of the relationship between exercise and adiponectin in humans have shown equivocal findings [97,98].…”

NPFFR2-deficient mice fed a high-fat diet develop strong intolerance to glucose

“…Even short-term HFD feeding causes structural and functional changes in the mediobasal hypothalamus, thus affecting caloric intake, energy expenditure, and systemic glucose tolerance [ 38 , 39 ]. Diet-induced obesity has been shown to be associated with a decrease in both leptin and insulin signaling in the hypothalamus [ 40 , 41 ]. Even though NPFFR2 deletion did not alter plasma insulin in fasted animals in the present study, NPFFR2 KO mice displayed imperfect brain PI3K/Akt signaling owing to decreased insulin signaling proteins in the hypothalamus and brainstem, two essential regions regulating energy metabolism, after feeding a HFD for 17 weeks.…”