Oxidative phenotype induced by aerobic physical training prevents the obesity-linked insulin resistance without changes in gastrocnemius muscle ACE2-Angiotensin(1-7)-Mas axis.

BACKGROUND: We investigate the effect of aerobic physical training (APT) on muscle morphofunctional markers and Angiotensin Converting Enzyme 2/Angiotensin 1-7/Mas receptor (ACE2/Ang 1-7/Mas) axis in an obesity-linked insulin resistance (IR) animal model induced by cafeteria diet (CAF). METHODS: Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR (chow diet, trained; n = 10), CAF-SED (n = 10) and CAF-TR (n = 10). APT consisted in running sessions of 60 min at 60% of maximal speed, 5 days per week for 8 weeks. RESULTS: Trained groups had lower body weight and adiposity compared with sedentary groups. CAF-TR improved the glucose and insulin tolerance tests compared with CAF-SED group (AUC = 28.896 ± 1589 vs. 35.200 ± 1076 mg dL-1 120 min-1; kITT = 4.1 ± 0.27 vs. 2.5 ± 0.28% min-1, respectively). CHOW-TR and CAF-TR groups increased exercise tolerance, running intensity at which VO2 max was reached, the expression of p-AMPK, p-ACC and PGC1-α proteins compared with CHOW-SED and CAF-SED. Mithocondrial protein expression of Mfn1, Mfn2 and Drp1 did not change. Lipid deposition reduced in CAF-TR compared with CAF-SED group (3.71 vs. 5.53%/area), but fiber typing, glycogen content, ACE2 activity, Ang 1-7 concentration and Mas receptor expression did not change. CONCLUSIONS: The APT prevents obesity-linked IR by modifying the skeletal muscle phenotype to one more oxidative independent of changes in the muscle ACE2/Ang 1-7/Mas axis.

Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse.

The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through ß-adrenergic receptors (AR). Here, we wished to define the role played by the ARß3 isoform in this process. This study focused on the ARß3 knockout mice (ARß3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARß3KO mice defend core temperature during cold exposure (4°C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, ARß3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in ARß3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in ARß3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, ARß3 inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.

Reversal of metabolic adaptations induced by physical training after two weeks of physical detraining.

The present study aimed to evaluate the effect of two weeks of physical detraining (PD) on energy balance components, white adipose tissue (WAT) metabolism, body weight (BW) and adiposity. Male C57BL/6J mice were assigned into groups sedentary (S, n = 20) and trained (T, n = 18). Physical training (PT) consisted of two 1.5 h daily sessions of swimming, 5 times/week for 4 weeks. After the PT, some of the S (S4, n = 10) and T (T4, n = 8) animals were sacrificed, and the others were kept sedentary (S6, n = 10) or detrained for two weeks (D, n = 10). After PT, the T group showed lower BW compared with S group, but PD reversed this response. The BW gains were 4%, 3% and 6.3% in S, S6 and D groups, respectively, however the T group decreased by 1.7%. T4 and D groups showed lower visceral fat depots and larger heart and left ventricle weights compared with S4 and S6 groups. Food intake, oxygen consumption at rest and fasting-induced weight loss were higher in T4 group compared with S4, and this was reversed by PD. Serum concentration of insulin, the activity of enzyme FAS and mean blood pressure did not differ among groups, but the concentration of leptin and resting heart rate were lower in T4 and D groups compared with S4 and S6 groups. T4 group increased lipolytic activity stimulated by isoproterenol and citrate synthase activity, which were reversed by PD. In conclusion, PD reversed the components of energy balance by reducing food intake and resting metabolism, and impaired WAT lipolytic activity, but not lipogenic activity. These changes resulted in remodeling of BW, but not adiposity.

Comparison between cafeteria and high-fat diets in the induction of metabolic dysfunction in mice.

This study sought to compare the metabolic responses induced by high-fat (HF) diet and cafeteria (CA) diet in mice. Adult male C57BL/6J mice were assigned into groups fed a chow (C, n=13), CA (n=12) or HF (n=11) diet during 12 weeks. Diets did not change body weight, Lee index, inguinal subcutaneous fat, the weight of organs and muscles, resting arterial pressure and heart rate. CA and HF increased visceral fat pad mass compared to C group, but only CA group showed greater adipocyte diameter and food intake compared to the C. Food intake was reduced in HF compared to C group. CA and HF showed hyperglycemia in the 3(rd), 6(th), 9(th) and 12(th) week and all values were higher in CA than HF, except in the 6(th) week. CA group showed glucose intolerance (GI) in the 6(th) week, while HF group did not show GI until the 9(th) week. CA decreased insulin sensitivity compared to C in the 12(th) week (kITT=3.3±0.2%/min vs. 4.2±0.1%/min). CA and HF groups presented higher insulin, leptin, total cholesterol, LDL-C, triglycerides and FFA levels compared to the C group. Total cholesterol and LDL-C in mg/dL were higher in the HF (161.9±7.2 and 57.5±13.4) than the CA (110.5±9.1 and 48.5±11.4), and HDL-C was higher in the HF than in the C and CA groups. In conclusion, the CA diet was more efficient to induce hyperphagia, adipocyte hypertrophy, hyperglycemia, earlier GI and insulin resistance, while the HF diet was more efficient to induce lipid profile changes.