Time-restricted feeding combined with aerobic exercise training can prevent weight gain and improve metabolic disorders in mice fed a high-fat diet.

KEY POINTS: Time-restricted feeding (TRF, in which energy intake is restricted to 8 h/day during the dark phase) alone or combined with aerobic exercise (AE) training can prevent weight gain and metabolic disorders in Swiss mice fed a high-fat diet. The benefits of TRF combined with AE are associated with improved hepatic metabolism and decreased hepatic lipid accumulation. TRF combined with AE training increased fatty acid oxidation and decreased expression of lipogenic and gluconeogenic genes in the liver of young male Swiss mice. TRF combined with AE training attenuated the detrimental effects of high-fat diet feeding on the insulin signalling pathway in the liver. ABSTRACT: Time-restricted feeding (TRF) or physical exercise have been shown to be efficient in the prevention and treatment of metabolic disorders; however, the additive effects of TRF combined with aerobic exercise (AE) training on liver metabolism have not been widely explored. In this study TRF (8 h in the active phase) and TRF combined with AE (TRF+Exe) were compared in male Swiss mice fed a high-fat diet, with evaluation of the effects on insulin sensitivity and expression of hepatic genes involved in fatty acid oxidation, lipogenesis and gluconeogenesis. As in previous reports, we show that TRF alone (eating only between zeitgeber time 16 and 0) was sufficient to reduce weight and adiposity gain, increase fatty acid oxidation and decrease lipogenesis genes in the liver. In addition, we show that mice of the TRF+Exe group showed additional adaptations such as increased oxygen consumption ( V̇O2${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ ), carbon dioxide production ( V̇CO2${\dot V_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ ) and production of ketone bodies (ß-hydroxybutyrate). Also, TRF+Exe attenuated the negative effects of high-fat diet feeding on the insulin signalling pathway (insulin receptor, insulin receptor substrate, Akt), and led to increased fatty acid oxidation (Ppara, Cpt1a) and decreased gluconeogenic (Fbp1, Pck1, Pgc1a) and lipogenic (Srebp1c, Cd36) gene expression in the liver. These molecular results were accompanied by increased glucose metabolism, lower serum triglycerides and reduced hepatic lipid content in the TRF+Exe group. The data presented in this study show that TRF alone has benefits but TRF+Exe has additive benefits and can mitigate the harmful effects of consuming a high-fat diet on body adiposity, liver metabolism and glycaemic homeostasis in young male Swiss mice.

Molecular mechanisms underlying fructose-induced cardiovascular disease: exercise, metabolic pathways and microRNAs.

NEW FINDINGS: What is the central question of this study? What are the mechanisms underlying the cardiac protective effect of aerobic training in the progression of a high fructose-induced cardiometabolic disease in Wistar rats? What is the main finding and its importance? At the onset of cardiovascular disease, aerobic training activates the p-p70S6K, ERK and IRß-PI3K-AKT pathways, without changing the miR-126 and miR-195 levels, thereby providing evidence that aerobic training modulates the insulin signalling pathway. These data contribute to the understanding of the molecular cardiac changes that are associated with physiological left ventricular hypertrophy during the development of a cardiovascular disease. ABSTRACT: During the onset of cardiovascular disease (CVD), disturbances in myocardial vascularization, cell proliferation and protein expression are observed. Aerobic training prevents CVD, but the underlying mechanisms behind left ventricle (LV) hypertrophy are not fully elucidated. The aim of this study was to investigate the mechanisms by which aerobic training protects the heart from LV hypertrophy during the onset of fructose-induced cardiometabolic disease. Male Wistar rats were allocated to four groups (n = 8/group): control sedentary (C), control training (CT), fructose sedentary (F) and fructose training (FT). The C and CT groups received drinking water, and the F and FT groups received d-fructose (10% in water). After 2 weeks, the CT and FT rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min/day, 4 days/week). After 10 weeks, LV morphological remodelling, cardiomyocyte apoptosis, microRNAs and the insulin signalling pathway were investigated. The F group had systemic cardiometabolic alterations, which were normalised by aerobic training. The LV weight increased in the FT group, myocardium vascularisation decreased in the F group, and the cardiomyocyte area increased in the CT, F and FT groups. Regarding protein expression, total insulin receptor ß-subunit (IRß) decreased in the F group; phospho (p)-IRß and phosphoinositide 3-kinase (PI3K) increased in the FT group; total-AKT and p-AKT increased in all of the groups; p-p70S6 kinase (p70S6K) protein was higher in the CT group; and p-extracellular signal-regulated kinase (ERK) increased in the CT and FT groups. MiR-126, miR-195 and cardiomyocyte apoptosis did not differ among the groups. Aerobic training activates p-p70S6K and p-ERK, and during the onset of a CVD, it can activate the IRß-PI3K-AKT pathway.