Physical exercise attenuates obesity development in Western-diet fed obese rats independently of vitamin D supplementation.

Physical inactivity, associated with the ingestion of hypercaloric foods, contributes to obesity development. In contrast, physical exercise training (ET) can slow obesity progression. Vitamin (Vit) D, a hormone that regulates adipocyte metabolism, may represent a strategy to reduce obesity; however, it is currently not known whether Vit D enhances the anti-obesity benefits of physical exercise. We hypothesized that swimming ET may prevent Western diet (WD)-induced obesity, and that Vit D supplementation could enhance the anti-obesity actions of ET. Male Wistar rats were fed, from 21 to 90 days of age, on a standard diet, or a WD, in association or not (sedentary control [CTL-SED] and WD [WD-SED] groups) with swimming ET for 15 min/day, 3 days a week (exercised CTL [CTL-EXE] and WD [WD-EXE] groups). Additionally, at 60 days of age, half of the CTL-EXE and WD-EXE groups were submitted, or not, to oral Vit D supplementation (CTL-EXE-VD and WD-EXE-VD groups, respectively). At 91 days old, WD-SED rats displayed increased body weight, abdominal adiposity, hypercholesterolemia, hyperleptinaemia and high circulating levels of tumour necrosis factor (TNF)-α. Swimming ET attenuated the increase in abdominal adiposity induced by WD. Furthermore, the WD-EXE group exhibited reductions in glycaemia, triglyceridaemia, cholesterolaemia, leptinaemia and in plasma TNF-α concentrations. Vitamin D supplementation, combined with ET, did not provide any additive benefit against adiposity, only potentiating the effects of ET action on the reduction in triglyceridaemia. Exercise training, independently of Vit D, provides a strategy to attenuate the adiposity expansion that is induced by WD, mediated in part by reductions in leptinaemia and TNF-α levels.

Moderate exercise restores pancreatic beta-cell function and autonomic nervous system activity in obese rats induced by high-fat diet.

BACKGROUND/AIMS: Metabolic syndrome has been identified as one of the most significant threats to human health in the 21(st) century. Exercise training has been shown to counteract obesity and metabolic syndrome. The present study aimed to investigate the effects of moderate exercise training on pancreatic beta-cell function and autonomic nervous system (ANS) activity in rats fed a high-fat diet (HFD). METHODS: Weaning rats were divided into four groups: rats fed a standard chow or HFD (sedentary, Control-SED and HFD-SED; or exercised, Control-EXE and HFD-EXE, respectively). Exercised rats ran (from 21- to 91-days-old) for 60 minutes (3 times/week) over a 10-week period. Glucose and insulin tolerance tests were performed. Pancreatic islets were isolated to study glucose-induced insulin secretion (GIIS). Parasympathetic and sympathetic nerve electrical signals were measured, and liver samples were processed and histologically analyzed. RESULTS: Exercise prevented obesity, insulin resistance, and liver steatosis as well as improved total cholesterol, ALT, and AST levels. Islets from HFD rats showed insulin hypersecretion which was ameliorated by exercise. Exercise decreased vagal nerve activity in the HFD-EXE group and increased the activity of the sympathetic nervous system in both exercised groups. CONCLUSION: Exercise prevents obesity and liver steatosis and restores pancreatic beta-cell function and ANS activity in HFD-obese rats.

Low-Intensity swimming training after weaning improves glucose and lipid homeostasis in MSG hypothalamic obese mice.

Low-intensity swimming training, started at an early age, was undertaken to observe glycemic control in hypothalamic obese mice produced by neonatal monosodium l-glutamate (MSG) treatment. Although swimming exercises by weaning pups inhibited hypothalamic obesity onset and recovered sympathoadrenal axis activity, this event was not observed when exercise training is applied to young adult mice. However, the mechanisms producing this improved metabolism are still not fully understood. Current work verifies whether, besides reducing fat tissue accumulation, low-intensity swimming in MSG-weaned mice also improves glycemic control. Although MSG and control mice swam for 15 min/day, 3 days a week, from the weaning stage up to 90 days old, sedentary MSG and normal mice did not exercise at all. After 14 h of fasting, animals were killed at 90 days of age. Retroperitonial fat accumulation was measured to estimate obesity. Fasting blood glucose and insulin concentrations were also measured. Mice were also submitted to ipGTT. MSG obese mice showed fasting hyperglycemia, hyperinsulinemia, and glucose intolerance and insulin resistance. However, the exercise was able to block MSG treatment effects. Higher total cholesterol and triglycerides observed in MSG mice were normalized by exercise after weaning. Exercised MSG animals had higher HDLc than the sedentary group. Data suggest that early exercise training maintains normoglycemia, insulin tissue sensitivity, and normal lipid profile in mice programmed to develop metabolic syndrome.

Vitamin D supplementation decreases visceral adiposity and normalizes leptinemia and circulating TNF-α levels in western diet-fed obese rats.

AIMS: Vitamin (Vit) D regulates various organic processes, including adipose tissue morphofunction and lipid metabolism. Studies indicate that Vit D bioavailability is reduced in obesity, which could contribute to obesity development; however, the effects of Vit D supplementation on increased adiposity in western diet (WD)-obese rats (an experimental model that better resembles the obesogenic human obesity condition) have not been studied, to date. Thus, we hypothesized that Vit D supplementation following the induction of obesity in WD rats might reduce their body weight (BW) and adiposity. MAIN METHODS: Male Wistar rats were fed on a standard chow [control (CTL) group] or a WD to induce obesity (WD group), from 21 to 59 days of age. Subsequently, from 60 to 90-days, half of the CTL and of the WD rats were randomly submitted, or not, to oral Vit D supplementation (CTL-VD and WD-VD groups, respectively). KEY FINDINGS: At 91 days of age, WD rats were obese, displaying higher abdominal circumference and white fat stores, dyslipidemia, hyperleptinemia and greater plasma levels of tumor necrosis factor (TNF)-α. Vit D supplementation decreased BW gain, abdominal fat deposition and ameliorated the plasma lipid profile in WD-VD rats. These effects were accompanied by reductions in leptinemia and in circulating TNF-α levels in these rodents. SIGNIFICANCE: Vit D supplementation, following the induction of obesity, may represent a good strategy to attenuate BW gain and abdominal adiposity, and ameliorate the plasma lipid profile in WD rats. These effects may be mediated, at least in part, by reductions in circulating levels of leptin and TNF-α.

Caloric restriction prevents alveolar bone loss in the experimental periodontitis in obese rats.

AIMS: It has been shown that periodontitis, can be modified by systemic changes, including behavioral factors, such as diet. Caloric restriction is one of the dietary therapeutic strategies indicated for obesity. It is associated with several benefits, among them, modulation of the inflammatory response. The aim of this study was to verify whether caloric restriction in obese rats changes the progression of experimental ligature-induced periodontitis. MATERIALS AND METHODS: Forty-eight Wistar rats were used for 24 weeks and initially fed with cafeteria diet during 12 weeks. The animals were divided into four groups according to the caloric restriction and experimental periodontitis. The cotton thread was placed around the mandibular first molars, for 15 days, before the end of the experiment. Rats submitted to caloric restriction received, from the 13th week of the experimental protocol, 70% of the food intake compared to the ad libitum animals of other study of the our research group. Alveolar bone loss was assessed using macroscopic morphometric analysis. Analyzes of clinical periodontal measures, biometrics, serum biomarkers and biochemical parameters were performed. KEY FINDINGS: Caloric restriction decreased the alveolar bone loss in the periodontitis group when compared to the group that received a cafeteria diet with periodontitis. Moreover, the results demonstrate the improvement in the glycemic profile, without prejudice to bone tissue biomarkers. SIGNIFICANCE: Based on the results, caloric restriction reduces the progression of alveolar bone loss in rats with experimental periodontitis, in addition to presenting benefits in biometric data, decreasing both glycemic profile and clinical periodontal measures.

Agreement, correlation, and kinetics of the alveolar bone-loss measurement methodologies in a ligature-induced periodontitis animal model.

Periodontal research involves the use of animal models to better understand the biological processes of periodontal diseases and the potential of new or existing therapies. Currently, ligature-induced periodontitis in rats is the main model used in periodontal research, in this model, alveolar bone loss (ABL) is the main parameter evaluated by radiographic, morphometric, and histological techniques. Interestingly, although these methodologies are widely used, it is not totally clarified neither the kinetics of ABL over the induction time nor the agreement degree (repeatability and reproducibility) of these techniques. OBJECTIVE: To characterize ABL kinetics at 0, 3, 7, 15, 30, and 60 days after ABL induction by ligature and to evaluate the intra- (repeatability) and inter-examiner (reproducibility) agreement and the correlation among the radiographic, morphometric, and histological methodologies. MATERIAL AND METHODS: 60 male Wistar rats with induced ABL were randomly divided into 6 experimental groups (n = 10 animals/group). After 0, 3, 7, 15, 30, and 60 days, the animals were euthanized and their hemimandibles were removed for ABL determination using radiographic, morphometric and histological techniques. RESULTS: Radiographic and morphometric/linear techniques allowed the detection of statistically significant ABL on the third day, while histological and morphometric/area techniques could only detect ABL after the seventh day (ANOVA/Tukey, p<0.05). After the fifteenth day, except for histological analysis, the ABL was stabilized. Concerning the agreement of the methodologies, Bland Altman's test (intra and inter-examiner evaluations) showed no difference among the measurements (p>0.05). In addition, high correlations (Pearson's test, r2>0.9, p<0.05) were observed. CONCLUSION: The results indicated that the minimum time for ABL induction could vary from 3 to 7 days, according to the chosen analysis methodology. Agreement and correlation data support the comparison of results between studies with same induction time.

Association Between Exercise and Treatment with Liraglutide in Obese Rats by Cafeteria Diet

Abstract The objective of this study was to evaluate the effect of liraglutide, an analog of glucagon-like peptide-1 (GLP-1) in association with physical exercise, on the metabolic and biochemical parameters of rats induced to obesity with a cafeteria diet. Male Wistar rats, aged 21 days, were randomly divided into: Controls (CON) receiving standard feed and water ad libitum; and obese (OBESE) receiving cafeteria diet ad libitum, added to the standard diet. Groups were then subdivided into: Liraglutide animals that received subcutaneous injections of liraglutide from 80 to 90 days of life; exercised (EXE) animals submitted to swimming sessions, three days a week (15 min); and liraglutide + EXE animals that received liraglutide in association with physical exercise. Treatment with liraglutide reduced deposits of mesenteric and periepididymal fat, HOMA-IR, triglycerides, glucose and insulin in obese group. It is important to note that the association of the two treatments reduced the body weight in animals, deposits of mesenteric and periepididymal fat, HOMA-IR, blood triglyceride levels, glucose and insulin in obese rats. As such, the association of liraglutide with exercise potentiated the effects of the drug and ameliorated obesity pathology more effectively. retirar

Low-intensity and moderate exercise training improves autonomic nervous system activity imbalanced by postnatal early overfeeding in rats.

BACKGROUND: Postnatal early overfeeding and physical inactivity are serious risk factors for obesity. Physical activity enhances energy expenditure and consumes fat stocks, thereby decreasing body weight (bw). This study aimed to examine whether low-intensity and moderate exercise training in different post-weaning stages of life is capable of modulating the autonomic nervous system (ANS) activity and inhibiting perinatal overfeeding-induced obesity in rats. METHODS: The obesity-promoting regimen was begun two days after birth when the litter size was adjusted to 3 pups (small litter, SL) or to 9 pups (normal litter, NL). The rats were organized into exercised groups as follows: from weaning until 90-day-old, from weaning until 50-day-old, or from 60- until 90-days-old. All experimental procedures were performed just one day after the exercise training protocol. RESULTS: The SL-no-exercised (SL-N-EXE) group exhibited excess weight and increased fat accumulation. We also observed fasting hyperglycemia and glucose intolerance in these rats. In addition, the SL-N-EXE group exhibited an increase in the vagus nerve firing rate, whereas the firing of the greater splanchnic nerve was not altered. Independent of the timing of exercise and the age of the rats, exercise training was able to significantly blocks obesity onset in the SL rats; even SL animals whose exercise training was stopped at the end of puberty, exhibited resistance to obesity progression. Fasting glycemia was maintained normal in all SL rats that underwent the exercise training, independent of the period. These results demonstrate that moderate exercise, regardless of the time of onset, is capable on improve the vagus nerves imbalanced tonus and blocks the onset of early overfeeding-induced obesity. CONCLUSIONS: Low-intensity and moderate exercise training can promote the maintenance of glucose homeostasis, reduces the large fat pad stores associated to improvement of the ANS activity in adult rats that were obesity-programmed by early overfeeding.

Agreement, correlation, and kinetics of the alveolar bone-loss measurement methodologies in a ligature-induced periodontitis animal model

Abstract Periodontal research involves the use of animal models to better understand the biological processes of periodontal diseases and the potential of new or existing therapies. Currently, ligature-induced periodontitis in rats is the main model used in periodontal research, in this model, alveolar bone loss (ABL) is the main parameter evaluated by radiographic, morphometric, and histological techniques. Interestingly, although these methodologies are widely used, it is not totally clarified neither the kinetics of ABL over the induction time nor the agreement degree (repeatability and reproducibility) of these techniques. Objective: To characterize ABL kinetics at 0, 3, 7, 15, 30, and 60 days after ABL induction by ligature and to evaluate the intra- (repeatability) and inter-examiner (reproducibility) agreement and the correlation among the radiographic, morphometric, and histological methodologies. Material and Methods: 60 male Wistar rats with induced ABL were randomly divided into 6 experimental groups (n = 10 animals/group). After 0, 3, 7, 15, 30, and 60 days, the animals were euthanized and their hemimandibles were removed for ABL determination using radiographic, morphometric and histological techniques. Results: Radiographic and morphometric/linear techniques allowed the detection of statistically significant ABL on the third day, while histological and morphometric/area techniques could only detect ABL after the seventh day (ANOVA/Tukey, p<0.05). After the fifteenth day, except for histological analysis, the ABL was stabilized. Concerning the agreement of the methodologies, Bland Altman's test (intra and inter-examiner evaluations) showed no difference among the measurements (p>0.05). In addition, high correlations (Pearson's test, r2>0.9, p<0.05) were observed. Conclusion: The results indicated that the minimum time for ABL induction could vary from 3 to 7 days, according to the chosen analysis methodology. Agreement and correlation data support the comparison of results between studies with same induction time.

Autonomic activity and glycemic homeostasis are maintained by precocious and low intensity training exercises in MSG-programmed obese mice.

Current research employed electrical records from superior vagus and sympathetic nerve branch that supply fat retroperitoneal tissue (RS nerve) to investigate whether very moderate swim training in obese-programmed mice would change sympathetic and parasympathetic autonomic nervous system activities. Neonatal mice were treated with monosodium L: -glutamate (MSG), during their first 5 days of life, to induce obesity. Mice started training on weaning, comprising free swimming 3 days/week, 15 min/day for 10 weeks. After 12 h fasting, the nerve electrical signals of the 90-day-old mice were processed to obtain firing rates. Blood samples were collected to measure glucose and insulin levels. Adrenal catecholamine content was measured. MSG treatment caused obesity. Hyperglycemia and hyperinsulinemia in MSG-obese mice, without any change in food intake, were obtained. Vagus firing rates were higher in obese mice than those in lean ones. A decrease in RS nerve activity and lower adrenal catecholamine stores have been observed. Swimming normalized blood glucose and insulin levels and MSG-obesity onset was attenuated by exercise. Vagus activity from obese mice decreased, whereas RS nerve activity and adrenal catecholamine levels increased in trained ones. Results suggest that autonomic activity imbalance and metabolic dysfunctions observed in MSG-obese mice were inhibited by precocious and moderate exercise training.

Efeito de um programa de exercício físico moderado em ratos de diferentes modelos de obesidade / Effect of moderate exercise program on rats from different models of obesity

A obesidade afeta uma parcela crescente da população mundial, acompanhada de distúrbios como a hipertensão e o diabetes tipo 2. Diversos modelos experimentais de obesidade foram criados para melhor entendê-la. Adicionalmente, o efeito do exercício físico na atenuação da obesidade vem sendo estudado. O objetivo do presente estudo foi avaliar o efeito de um programa de exercício físico moderado sobre a obesidade em três modelos experimentais: ninhada reduzida (NR), L-glutamato monosódico (MSG) e dieta hiperlipídica (DHL). Os ratos programados para a obesidade apresentaram diferenças significativas no peso corporal, no índice de Lee, no consumo de ração, na gordura corporal e na tolerância à glicose, se comparados ao grupo dos magros. O exercício físico foi capaz de impedir a instalação da obesidade e a deterioração do controle glicêmico. Os resultados sugerem que o treinamento físico moderado iniciado precocemente pode ser usado como prevenção ao desenvolvimento da obesidade e da síndrome metabólica.

Obesity has affected a growing part of world wild's population, accompanied by disorders such as hypertension and type 2 diabetes. Several experimental models of obesity have been created to better understand it. In addition, the effects of exercise training on animal obesity onset have been highlighted. The present study aimed to evaluate the effect of an exercise program of moderate intensity on obesity onset from three models: small litters (SL), monosodium L-glutamate (MSG) and high-fat diet (HFD). The sedentary obese rats showed significant differences in body weight, Lee's index, food intake, body fat and glucose tolerance compared with control group. However, exercise was able to inhibit obesity onset and to preserve glycemic homeostasis. We conclude that moderate physical exercise can be a tool to be used to prevent and control obesity and metabolic syndrome.

Pancreatic islets from hypothalamic obese rats maintain K+ATP channel-dependent but not -independent pathways on glucose-induced insulin release process.

One of the main features of obesity is hyperinsulinemia, which is related to insulin oversecretion. Glucose is by far the major physiological stimulator of insulin secretion. Glucose promotes an increase in the ATP/ADP ratio, which inactivates ATP-sensitive K+ channels (K+ATP) and induces beta cell depolarization with consequent calcium influx. Increased intracellular calcium concentration triggers insulin exocytosis. K+ATP channel function is important for K+ATP channel-dependent pathways involved in glucose-stimulated insulin secretion (GSIS). However, K+ATP channel-independent pathway has been identified and it has been found that this pathway sustains GSIS. Both pathways are critical to better GSIS control. GSIS was studied in pancreatic islets from hyperinsulinemic adult obese rats obtained by monosodium L-glutamate (MSG) neonatal treatment. Islets from MSG-obese rats were more glucose responsive than control ones. Diazoxide, a drug which maintains the K+ATP channels open without interfering with cell metabolism, blocked GSIS in islets from both groups. High extracellular potassium concentration plus diazoxide was used to study an alternative to the K+ATP channel pathway; in these conditions islets from MSG-obese rats did not respond, while islets from control animals showed enhanced GSIS. Results indicate that MSG-obese rats oversecreted insulin, even though the K+ATP channel-independent pathway is impaired in their beta cells.

The dual effect of isoproterenol on insulin release is suppressed in pancreatic islets from hypothalamic obese rats.

Hyperinsulinemia in obesity has been attributed to insulin oversecretion by pancreatic beta-cells. Beta-cells are equipped with cholinergic and adrenergic receptors; whereas overall acetylcholine action is to potentiate, catecholamines' effect is to inhibit glucose-induced insulin release (GIIR) via alpha2-adrenoceptor. However, it has been shown that beta-adrenergic agonists potentiate glucose response. GIIR was studied in pancreatic islets from hyperinsulinemic adult obese rats, obtained by L-glutamate monosodium (MSG) neonatal treatment. Islets from MSG-rats were more glucose responsive than control ones. Isoproterenol, a beta-adrenergic agonist, inhibited the GIIR in islets from MSG-obese rats. Results indicate that MSG treatment causes alteration on function of beta-cell adrenoceptors.