Moderate exercise training does not prevent the reduction in myocardial L-type Ca(2+) channels protein expression at obese rats (original) (raw)
Related papers
Hypertension, 2010
Previous studies show that exercise training and caloric restriction improve cardiac function in obesity. However, the molecular mechanisms underlying this effect on cardiac function remain unknown. Thus, we studied the effect of exercise training and/or caloric restriction on cardiac function and Ca 2ϩ handling protein expression in obese rats. To accomplish this goal, male rats fed with a high-fat and sucrose diet for 25 weeks were randomly assigned into 4 groups: high-fat and sucrose diet, high-fat and sucrose diet and exercise training, caloric restriction, and exercise training and caloric restriction. An additional lean group was studied. The study was conducted for 10 weeks. Cardiac function was evaluated by echocardiography and Ca 2ϩ handling protein expression by Western blotting. Our results showed that visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels were higher in rats on the high-fat and sucrose diet compared with the lean rats. Cardiac nitrate levels, reduced/oxidized glutathione, left ventricular fractional shortening, and protein expression of phosphorylated Ser 2808 -ryanodine receptor and Thr 17phospholamban were lower in rats on the high-fat and sucrose diet compared with lean rats. Exercise training and/or caloric restriction prevented increases in visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels and prevented reduction in cardiac nitrate levels and reduced:oxidized glutathione ratio. Exercise training and/or caloric restriction prevented reduction in left ventricular fractional shortening and in phosphorylation of the Ser 2808 -ryanodine receptor and Thr 17 -phospholamban. These findings show that exercise training and/or caloric restriction prevent cardiac dysfunction in high-fat and sucrose diet rats, which seems to be attributed to decreased circulating neurohormone levels. In addition, this nonpharmacological paradigm prevents a reduction in the Ser 2808 -ryanodine receptor and Thr 17phospholamban phosphorylation and redox status. (Hypertension. 2010;56:629-635.)
Brazilian Journal of Medical and Biological Research, 2019
Obesity is often associated with changes in cardiac function; however, the mechanisms responsible for functional abnormalities have not yet been fully clarified. Considering the lack of information regarding high-saturated-fat diet-induced obesity, heart function, and the proteins involved in myocardial calcium (Ca 2+) handling, the aim of this study was to test the hypothesis that this dietary model of obesity leads to cardiac dysfunction resulting from alterations in the regulatory proteins of intracellular Ca 2+ homeostasis. Male Wistar rats were distributed into two groups: control (C, n=18; standard diet) and obese (Ob, n=19; high-saturated-fat diet), which were fed for 33 weeks. Cardiac structure and function were evaluated using echocardiographic and isolated papillary muscle analyses. Myocardial protein expressions of sarcoplasmic reticulum Ca 2+-ATPase, phospholamban (PLB), PLB serine-16 phosphorylation, PLB threonine-17 phosphorylation, ryanodine receptor, calsequestrin, Na + /Ca 2+ exchanger, and L-type Ca 2+ channel were assessed by western blot. Obese rats presented 104% increase in the adiposity index (C: 4.5 ± 1.4 vs Ob: 9.2 ± 1.5%) and obesity-related comorbidities compared to control rats. The left atrium diameter (C: 5.0±0.4 vs Ob: 5.5±0.5 mm) and posterior wall shortening velocity (C: 36.7±3.4 vs Ob: 41.8±3.8 mm/s) were higher in the obese group than in the control. The papillary muscle function was similar between the groups at baseline and after inotropic and lusitropic maneuvers. Obesity did not lead to changes in myocardial Ca 2+ handling proteins expression. In conclusion, the hypothesis was not confirmed, since the high-saturated-fat diet-induced obese rats did not present cardiac dysfunction or impaired intracellular Ca 2+ handling proteins.
Life Sciences, 2020
We investigated the effects of high-intensity interval and continuous short-term exercise on body composition and cardiac function after myocardial ischemia-reperfusion injury (IRI) in obese rats. Methods: Rats fed with a standard chow diet (SC) or high-fat diet (HFD) for 20 weeks underwent systolic blood pressure (SBP), glycemia and dual-energy X-ray absorptiometry analyses. Then, animals fed with HFD were subdivided into three groups: sedentary (HFD-SED); moderate-intensity continuous training (HFD-MICT); and high-intensity interval training (HFD-HIIT). Exercised groups underwent four isocaloric aerobic exercise sessions, in which HFD-MICT maintained the intensity continuously and HFD-HIIT alternated it. After exercise sessions, all groups underwent global IRI and myocardial infarct size (IS) was determined histologically. Fat and muscle mass were weighted, and protein levels involved in muscle metabolism were assessed in skeletal muscle. Results: HFD-fed versus SC-fed rats reduced lean body mass by 31% (P < 0.001), while SBP, glycemia and body fat percentage were increased by 10% (P = 0.04), 30% (P = 0.006) and 54% (P < 0.001); respectively. HFDinduced muscle atrophy was restored in exercised groups, as only HFD-SED presented lower gastrocnemius (32%; P = 0.001) and quadriceps mass (62%; P < 0.001) than SC. PGC1-α expression was 2.7-fold higher in HFD-HIIT versus HFD-SED (P = 0.04), whereas HFD-HIIT and HFD-MICT exhibited 1.7-fold increase in p-mTOR Ser2481 levels compared to HFD-SED (P = 0.04). Although no difference was detected among groups for IS (P = 0.30), only HFD-HIIT preserved left-ventricle developed pressure after IRI (+0.7 mmHg; P = 0.9). Significance: Short-term exercise, continuous or HIIT, restored HFD-induced muscle atrophy and increased mTOR expression, but only HIIT maintained myocardial contractility following IRI in obese animals.
Frontiers in Physiology, 2019
We aimed to test whether moderate physical training can induce long-lasting protection against cardiovascular risk factors induced by high fat diet (HFD) intake, even after cessation of training. 90-days-old Wistar rats were submitted to a sedentary lifestyle or moderate physical training, three times a week, for 30 days. Following this, at 120 days-of age, sedentary and trained rats received a hypercaloric diet (HFD) or a commercial diet normal fat diet (NFD) for 30 days. Body weight (BW) and food intake were evaluated weekly. At 150 days-of age, hemodynamic measures (systolic, diastolic, mean blood pressure, pulse pressure, pulse interval and heart rate) were made via an indwelling femoral artery catheter. Beat-to-beat data were analyzed to calculate power spectra of systolic blood pressure (SBP) and pulse interval. After euthanasia, mesenteric fat pads were removed and weighted and total blood was stored for later analysis of lipid profile. Consumption of a HFD increased blood pressure (BP), pulse pressure, low frequency BP variability, BW gain, fat pad stores and induced dyslipidemia. Interestingly, prior physical training was able to partially protect against this rise in BP and body fat stores. Prior physical training did not totally protect against the effects of HFD consumption but previously trained animals did demonstrate resistance to the development of cardiometabolic alterations, which illustrate that the benefits of physical training may be partially maintained even after 30 days of detraining period.
Obesity induces upregulation of genes involved in myocardial Ca2+ handling
Brazilian Journal of Medical and Biological Research, 2008
Obesity is a complex multifactorial disorder that is often associated with cardiovascular diseases. Research on experimental models has suggested that cardiac dysfunction in obesity might be related to alterations in myocardial intracellular calcium (Ca 2+ ) handling. However, information about the expression of Ca 2+ -related genes that lead to this abnormality is scarce. We evaluated the effects of obesity induced by a high-fat diet in the expression of Ca 2+ -related genes, focusing the L-type Ca 2+ channel (Cacna1c), sarcolemmal Na + /Ca 2+ exchanger (NCX), sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a), ryanodine receptor (RyR2), and phospholamban (PLB) mRNA in rat myocardium. Male 30-day-old Wistar rats were fed a standard (control) or high-fat diet (obese) for 15 weeks. Obesity was defined as increased percent of body fat in carcass. The mRNA expression of Ca 2+ -related genes in the left ventricle was measured by RT-PCR. Compared with control rats, the obese rats had increased percent of body fat, area under the curve for glucose, and leptin and insulin plasma concentrations. Obesity also caused an increase in the levels of SERCA2a, RyR2 and PLB mRNA (P < 0.05) but did not modify the mRNA levels of Cacna1c and NCX. These findings show that obesity induced by high-fat diet causes cardiac upregulation of Ca 2+ transport-related genes in the sarcoplasmic reticulum.
Food restriction promotes downregulation of myocardial L-type Ca 2+ channels
Canadian Journal of Physiology and Pharmacology, 2009
Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca 2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca 2+ channels. Male 60-day-old Wistar rats were fed a control or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca 2+ channels was determined by using a pharmacological Ca 2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca 2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca 2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca 2+ channels.
Exercise training increases myocardial inotropic response in food restricted rats
International Journal of Cardiology, 2006
This study evaluated the effects of exercise training on myocardial function and ultrastructure of rats submitted to different levels of food restriction (FR). Male Wistar -Kyoto rats, 60 days old, were submitted to free access to food, light FR (20%), severe FR (50%) and/or to swimming training (one hour per day with 5% of load, five days per week for 90 days). Myocardial function was evaluated by left ventricular papillary muscle under basal condition (calcium 1.25 mM), and after extracellular calcium elevation to 5.2 mM and isoproterenol (1 AM) addition. The ultrastructure of the myocardium was examined in the papillary muscle. The training effectiveness was verified by improvement of myocardial metabolic enzyme activities. Both 20% and 50% food restriction protocols presented minor body and ventricular weights gain. The 20%-FR, in sedentary or trained rats, did not alter myocardial function or ultrastructure. The 50%-FR, in sedentary rats, caused myocardial dysfunction under basal condition, decreased response to inotropic stimulation, and promoted myocardial ultrastructural damage. The 50%-FR, in exercised rats, increased myocardial dysfunction under basal condition but increased response to inotropic stimulation although there was myocardial ultrastructural damage. In conclusion, the exercise training in severe restriction caused marked myocardial dysfunction at basal condition but increased myocardial response to inotropic stimulation. D
The Journal of biological chemistry, 2017
The transient receptor potential canonical channel-1 (TRPC1) is a Ca2+-permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle. Loss of TRPC1 may alter the regulation of cellular energy metabolism resulting in insulin resistance thereby leading to diabetes. Exercise reduces insulin resistance, but it is not known whether TRPC1 is involved in exercise-induced insulin sensitivity. The role of TRPC1 in adiposity and obesity-associated metabolic diseases has not yet been determined. Our results show that TRPC1 functions as a major Ca2+ entry channel in adipocytes. We have also shown that fat mass and fasting glucose concentrations were lower in TRPC1 KO mice that were fed a high-fat (HF) (45% fat) diet and exercised as compared with WT mice fed a HF diet and exercised. Adipocyte numbers were decreased in both subcutaneous and visceral adipose tissue of TRPC1 KO mice fed a HF diet and exercised. Finally, autophagy marke...
Influence of Long-Term Obesity on Myocardial Gene Expression
Arquivos Brasileiros de Cardiologia, 2013
Background: Several authors have shown that deterioration of cardiac function is associated with the degree and duration of obesity. It is necessary to establish the gene expression patterns after prolonged periods of obesity. Objective: This study tested the hypothesis that increased duration of exposure to obesity leads to a reduction in the mRNA levels of proteins involved in regulation of myocardial Ca 2+ homeostasis. In addition, this study verified whether the decrease in mRNA expression was caused by a reduction in thyroid hormone. Methods: Thirty-day-old male Wistar rats were distributed in two groups: control (C) and obese (Ob). The C group was fed a standard diet and the Ob was fed with high-fat diets for 15, 30 and 45 weeks. Obesity was defined by adiposity index. The gene expression was assessed by quantitative real-time PCR. Results: The adiposity index was higher in the Ob compared to the C after all periods. While obesity at 15 and 45 weeks resulted in a reduction in mRNA of sarcoplasmic reticulum Ca 2+-ATPase (SERCA2a), Na + /Ca 2+ exchanger (NCX), and calsequestrin (CSQ), L-type Ca 2+ channels, ryanodine receptor, SERCA2a, phospholamban (PLB), NCX, and CSQ expression were increased compared to the C after 30 weeks. There was no significant association between T3 levels and mRNA expression. Conclusions: Our data indicate that obesity over the short and long periods of time may promote alteration in gene expression of Ca 2+ homeostasis regulatory proteins without influence by thyroid hormone (Arq Bras Cardiol. 2013;100(3):229-237).