RESUMO
We tested the hypothesis that third ventricular (3V) injections of angiotensin 1-7 (Ang 1-7) increases thermogenesis in brown adipose tissue (BAT), and whether the Mas receptor mediates this response. First, in male Siberian hamsters (n = 18), we evaluated the effect of Ang 1-7 in the interscapular BAT (IBAT) temperature and, using selective Mas receptor antagonist A-779, the role of Mas receptor in this response. Each animal received 3V injections (200 nL), with 48 h intervals: saline; Ang 1-7 (0.03, 0.3, 3, and 30 nmol); A-779 (3 nmol); and Ang 1-7 (0.3 nmol) + A-779 (3 nmol). IBAT temperature increased after 0.3 nmol Ang 1-7 compared with Ang 1-7 + A-779 at 20, 30, and 60 min. Also, 0.3 nmol Ang 1-7 increased IBAT temperature at 10 and 20 min, and decreased at 60 min compared with pretreatment. IBAT temperature decreased after A-779 at 60 min and after Ang 1-7 + A-779 at 30 and 60 min compared with the respective pretreatment. A-779 and Ang 1-7 + A-779 decreased core temperature at 60 min compared with 10 min. Then, we evaluated blood and tissue Ang 1-7 levels, and the expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in IBAT. Male Siberian hamsters (n = 36) were killed 10 min after one of the injections. No changes were observed in blood glucose, serum and IBAT Ang 1-7 levels, and ATGL. Ang 1-7 (0.3 nmol) increased p-HSL expression compared with A-779 and increased p-HSL/HSL ration compared with other injections. Ang 1-7 and Mas receptor immunoreactive cells were found in brain regions that coincide with the sympathetic nerves outflow to BAT. In conclusion, 3V injection of Ang 1-7 induced thermogenesis in IBAT in a Mas receptor-dependent manner.
Assuntos
Tecido Adiposo Marrom , Phodopus , Cricetinae , Animais , Masculino , Tecido Adiposo Marrom/metabolismo , Termogênese/fisiologia , Sistema Nervoso Simpático/fisiologiaRESUMO
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; nâ¯=â¯13), CHOW-TR (chow diet, trained; nâ¯=â¯13), CAF-SED (cafeteria diet, sedentary; nâ¯=â¯13) and CAF-TR (cafeteria diet, trained; nâ¯=â¯13). AET consisted in running sessions of 60â¯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⯱â¯0.5%/area) compared with CHOW-SED (1.7⯱â¯0.54%/area), and the AET prevented this increase in the CAF-TR group (2.1⯱â¯0.5%/area). The Bowman's 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-α, ACC and p-ACC. ß-HAD activity increased in CAF-SED (43.9⯱â¯4.57â¯nmol·min-1·ug-1) and CAF-TR (44.7⯱â¯2.6â¯nmol·min-1·ug-1) groups compared to CHOW-SED (35.1⯱â¯2.9â¯nmol·min-1·ug-1) e CHOW-TR (36.6⯱â¯2.7â¯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.
Assuntos
Dieta , Hiperlipidemias/terapia , Rim/metabolismo , Rim/patologia , Metabolismo dos Lipídeos , Lipídeos/análise , Condicionamento Físico Animal , Animais , Peso Corporal , Hiperlipidemias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
AIM: This study sought to determine the role of white adipose tissue (WAT) metabolism in the prevention of insulin resistance (IR) by physical training (PT). MAIN METHODS: Male 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. KEY FINDINGS: PT 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. SIGNIFICANCE: The 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.
Assuntos
Tecido Adiposo Branco/metabolismo , Resistência à Insulina/fisiologia , Esforço Físico/fisiologia , Adipócitos/metabolismo , Adiponectina/sangue , Adiposidade , Animais , Ácidos Graxos não Esterificados/sangue , Intolerância à Glucose/prevenção & controle , Hiperglicemia/prevenção & controle , Hiperinsulinismo/prevenção & controle , Isoproterenol/farmacologia , Leptina/sangue , Lipólise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Condicionamento Físico Animal , Aumento de PesoRESUMO
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 ± 0.28 g, 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 ± 0.3 g/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 ± 0.12 ng/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.
Assuntos
Animais , Masculino , Camundongos , Tecido Adiposo Branco/metabolismo , Regulação da Expressão Gênica , Condicionamento Físico Animal/fisiologia , Aumento de Peso/genética , Adipogenia/genética , Adiponectina/genética , Marcadores Genéticos/genética , Leptina/genética , Lipogênese/genética , Lipólise/genéticaRESUMO
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 ± 0.28 g, 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 ± 0.3 g/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 ± 0.12 ng/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.
Assuntos
Tecido Adiposo Branco/metabolismo , Regulação da Expressão Gênica , Condicionamento Físico Animal/fisiologia , Aumento de Peso/genética , Adipogenia/genética , Adiponectina/genética , Animais , Marcadores Genéticos/genética , Leptina/genética , Lipogênese/genética , Lipólise/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C)ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Modelos Genéticos , Receptores Adrenérgicos alfa 2/genética , Sistema Renina-Angiotensina/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Angiotensina II/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Angiotensinogênio/metabolismo , Animais , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Frequência Cardíaca/fisiologia , Losartan/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Norepinefrina/sangue , Condicionamento Físico Animal , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/fisiologiaRESUMO
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.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Bradicardia/fisiopatologia , Frequência Cardíaca/fisiologia , Condicionamento Físico Animal/fisiologia , Descanso/fisiologia , Animais , Masculino , Consumo de Oxigênio/fisiologia , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
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 percent 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 percent when compared to PET and S rats, respectively. Detraining reduced peak VO2 in both D1 and D2 rats by 22 percent 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.
Assuntos
Animais , Masculino , Ratos , Sistema Nervoso Autônomo/fisiologia , Bradicardia/fisiopatologia , Frequência Cardíaca/fisiologia , Condicionamento Físico Animal/fisiologia , Descanso/fisiologia , Consumo de Oxigênio/fisiologia , Distribuição Aleatória , Ratos WistarRESUMO
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.
Assuntos
Cardiomegalia/etiologia , Condicionamento Físico Animal , Natação , Adaptação Fisiológica , Animais , Pressão Sanguínea , Cardiomegalia/patologia , Citrato (si)-Sintase/metabolismo , Frequência Cardíaca , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/enzimologia , Resistência Física , Fatores de TempoRESUMO
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 percent 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 percent). Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58 percent) 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 percent) and myocyte dimension (13-20 percent) 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.