F.S. Evangelista

Duration-controlled swimming exercise training induces cardiac hypertrophy in mice

Exercise training associated with robust conditioning can be useful for the study of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A swimming apparatus is described to control training regimens in terms of duration, load, and frequency of exercise. Mice were submitted to 60- vs 90-min session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood pressure was unchanged in all groups while resting heart rate decreased in the trained groups (8-18%). Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58%) only as a result of duration and frequency-controlled exercise training, indicating that endurance conditioning was obtained. In groups which received duration and endurance conditioning, cardiac weight (14-25%) and myocyte dimension (13-20%) increased. The best conditioning protocol to promote physiological hypertrophy, our primary goal in the present study, was 90 min, twice a day, 5 days a week for 4 weeks with no overload attached to the body. Thus, duration- and frequency-controlled exercise training in mice induces a significant conditioning response qualitatively similar to that observed in humans.

Loss of resting bradycardia with detraining is associated with intrinsic heart rate changes

The mechanisms underlying the loss of resting bradycardia with detraining were studied in rats. The relative contribution of autonomic and non-autonomic mechanisms was studied in 26 male Wistar rats (180-220 g) randomly assigned to four groups: sedentary (S, N = 6), trained (T, N = 8), detrained for 1 week (D1, N = 6), and detrained for 2 weeks (D2, N = 6). T, D1 and D2 were treadmill trained 5 days/week for 60 min with a gradual increase towards 50% peak VO2. After the last training session, D1 and D2 were detrained for 1 and 2 weeks, respectively. The effect of the autonomic nervous system in causing training-induced resting bradycardia and in restoring heart rate (HR) to pre-exercise training level (PET) with detraining was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. T rats significantly increased peak VO2 by 15 or 23.5% when compared to PET and S rats, respectively. Detraining reduced peak VO2 in both D1 and D2 rats by 22% compared to T rats, indicating loss of aerobic capacity. Resting HR was significantly lower in T and D1 rats than in S rats (313 +/- 6.67 and 321 +/- 6.01 vs 342 +/- 12.2 bpm) and was associated with a significantly decreased intrinsic HR (368 +/- 6.1 and 362 +/- 7.3 vs 390 +/- 8 bpm). Two weeks of detraining reversed the resting HR near PET (335 +/- 6.01 bpm) due to an increased intrinsic HR in D2 rats compared with T and D1 rats (376 +/- 8.8 bpm). The present study provides the first evidence of intrinsic HR-mediated loss of resting bradycardia with detraining in rats.

Remodeling of white adipose tissue metabolism by physical training prevents insulin resistance

AIMnThis study sought to determine the role of white adipose tissue (WAT) metabolism in the prevention of insulin resistance (IR) by physical training (PT).nnnMAIN METHODSnMale C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n=15), CHOW-TR (chow diet, trained; n=18), CAF-SED (cafeteria diet, sedentary; n=15) and CAF-TR (cafeteria diet, trained; n=18). PT consisted of running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks.nnnKEY FINDINGSnPT prevented body weight and fat mass accretion in trained groups and prevented hyperglycemia, hyperinsulinemia, glucose intolerance and IR in the CAF-TR. The CAF-SED group presented higher leptin and free fatty acid and lower adiponectin serum levels compared with other groups. Lipolytic activity (in mmol/10(6) adipose cells) stimulated by isoproterenol increased in CHOW-TR (16347±3005), CAF-SED (18110±3788) and CAF-TR (15837±2845) compared with CHOW-SED (8377±2284). The CAF-SED group reduced FAS activity compared with CHOW-SED and CHOW-TR, reduced citrate synthase activity and increased DGAT2 content compared with other groups. Both trained groups reduced G6PDH activity and increased the expression of p-AMPK (Thr172) compared with sedentary groups. CAF-SED group had lower levels of AMPK, p-AMPK (Thr172), ACC and p-ACC (Ser79) compared with other groups.nnnSIGNIFICANCEnThe prevention of IR by PT is mediated by adaptations in WAT metabolism by improving lipolysis, preventing an increase in enzymes responsible for fatty acid esterification and by activating enzymes that improve fat oxidation instead of fat storage.

Physical training prevents body weight gain but does not modify adipose tissue gene expression

The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28u2005g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3u2005g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12u2005ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.

Exposure to high-fat diet since post-weaning induces cardiometabolic damage in adult rats.

AIMSnThis study sought to investigate the metabolic, hemodynamic and autonomic responses in adult rats exposed to high-fat diet since post-weaning.nnnMAIN METHODSnYoung male Wistar rats were assigned into groups fed with standard normal diet (3% lipids; ND, n=8) or high-fat diet (30% lipids; HD, n=8) during 8weeks. Body composition, food intake, serum triglycerides, total cholesterol, insulin, leptin and adiponectin concentrations were determined. Hemodynamic and autonomic evaluations were performed. Renin angiotensin system and nitric oxide were also studied by pharmacological blockades.nnnKEY FINDINGSnHD group showed no difference in body weight, total cholesterol, food intake in calories and insulin concentration, but visceral fat pads weight, triglycerides and leptin were higher in HD group. Moreover, HD group decreased adiponectin level, increased 12% of mean arterial pressure (MAP) and 6% of heart rate compared with ND group. Spectral analyses showed an increase in cardiovascular sympathetic modulation in HD compared with ND group. Depressor responses after losartan were higher in HD compared with ND group: -9±0.7 vs.-3±1.6mmHg. Pressor responses after l-NAME were higher in HD compared with ND: 45±8 vs. 32±5mmHg.nnnSIGNIFICANCEnHigh-fat diet consumption during early period of life can increase WAT mass and MAP. These alterations may be mediated by an augment in sympathetic activity associated with higher leptin and lower adiponectin levels. These cardiometabolic damages can lead to the development of hypertension and increase cardiovascular risk in adulthood.

Aerobic exercise training prevents kidney lipid deposition in mice fed a cafeteria diet

Aim: The objective of this study was to investigate the potential of aerobic exercise training (AET) to prevent kidney lipid accumulation and the contribution of renal metabolism to mediate this response. Main methods: Male C57BL/6J mice were assigned into groups CHOW‐SED (chow diet, sedentary; n = 13), CHOW‐TR (chow diet, trained; n = 13), CAF‐SED (cafeteria diet, sedentary; n = 13) and CAF‐TR (cafeteria diet, trained; n = 13). AET consisted in running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks. Key findings: AET prevented weight gain in both trained groups. Food intake was not different among groups, however water intake, urine output, urine potassium and osmolarity were reduced in CAF‐SED and CAF‐TR groups. Kidney lipid deposition increased in CAF‐SED (4.12 ± 0.5%/area) compared with CHOW‐SED (1.7 ± 0.54%/area), and the AET prevented this increase in the CAF‐TR group (2.1 ± 0.5%/area). The Bowmans capsule area decreased in CAF‐SED and CAF‐TR groups while the Bowman space reduced in CAF‐SED compared to CHOW‐SED group, which was prevented by AET in the CAF‐TF group. We observed a 27% increase in the p‐AMPK expression in CAF‐TR compared to CHOW‐SED group without differences in the SIRT‐1, PGC1‐&agr;, ACC and p‐ACC. &bgr;‐HAD activity increased in CAF‐SED (43.9 ± 4.57 nmol·min−1·ug−1) and CAF‐TR (44.7 ± 2.6 nmol·min−1·ug−1) groups compared to CHOW‐SED (35.1 ± 2.9 nmol·min−1·ug−1) e CHOW‐TR (36.6 ± 2.7 nmol·min−1·ug−1). Significance: AET prevented kidney lipid accumulation induced by cafeteria diet and this response was not associated with changes in the renal metabolic activity that favors lipid oxidation.

ACE-modulated adiposity is related to higher energy expenditure and independent of lipolysis and glucose incorporation into lipids in adipocytes

Emerging evidence suggests that both systemic and white adipose tissue-renin-angiotensin system components influence body weight control. We previously demonstrated that higher angiotensin-converting enzyme (ACE) gene expression is associated with lower body adiposity in a rodent model. In this study, we tested the hypothesis that a higher ACE gene dosage reduces fat accumulation by increasing energy expenditure and modulating lipolysis and glucose incorporation into lipids in adipocytes. After a 12 wk follow-up period, transgenic mice harboring three ACE (3ACE) gene copies displayed diminished WAT mass, lipid content in their carcasses, adipocyte hypotrophy, and higher resting oxygen uptake (V̇o2) in comparison with animals with one ACE gene copy (1ACE) after long fasting (12 h). No differences were found in food intake and in the rates of lipolysis and glucose incorporation into lipids in adipocytes. To assess whether this response involves increased angiotensin II type I receptor (AT1R) activation, AT1R blocker (losartan) was used in a separate group of 3ACE mice with body weight and adiposity comparable to that in the other 3ACE animals. We suggest that fasting-induced lower adiposity observed in animals with 3ACE gene copies might be associated with a higher expense of energy reserves; this response did not involve AT1R activation.