Tatiane Aparecida Ribeiro

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 21st 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-protein diet in adult male rats has long-term effects on metabolism.

Nutritional insults during developmental plasticity have been linked with metabolic diseases such as diabetes in adulthood. We aimed to investigate whether a low-protein (LP) diet at the beginning of adulthood is able to program metabolic disruptions in rats. While control rats ate a normal-protein (23%; NP group) diet, treated rats were fed a LP (4%; LP group) diet from 60 to 90 days of age, after which an NP diet was supplied until they were 150 days old. Plasma levels of glucose and insulin, autonomous nervous system (ANS), and pancreatic islet function were then evaluated. Compared with the NP group, LP rats exhibited unchanged body weight and reduced food intake throughout the period of protein restriction; however, after the switch to the NP diet, hyperphagia of 10% (P<0.05), and catch-up growth of 113% (P<0.0001) were found. The LP rats showed hyperglycemia, insulin resistance, and higher fat accretion than the NP rats. While the sympathetic tonus from LP rats reduced by 28%, the vagus tonus increased by 21% (P<0.05). Compared with the islets from NP rats, the glucose insulinotropic effect as well as cholinergic and adrenergic actions was unaltered in the islets from LP rats. Protein restriction at the beginning of adulthood induced unbalanced ANS activity and fat tissue accretion later in life, even without functional disturbances in the pancreatic islets.

Vagus nerve contributes to metabolic syndrome in high-fat diet-fed young and adult rats

What is the central question of this study? Differentnerve contributes periods of life are known for their differential sensitivity to interventions, and increased parasympathetic activity affects the development and maintenance of obesity. Thus, we evaluated the involvement of the vagus nerve by performing a vagotomy in young or adult rats that were offered an obesogenic high‐fat diet. What is the main finding and its importance? Although the accumulation of adipose tissue decreased in both younger and older groups, the younger rats showed a greater response to the effects of vagotomy in general. In addition to the important role of the parasympathetic activity, we suggest that the vagus nerve contributes to the condition of obesity.

Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

Background/Aims: Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Methods: Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Results: Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C) and dark (NL 38°C vs. SL 37.6°C) periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (p<0.01), and no difference was observed in the sympathetic nerve activity. In adulthood, the small litter rats were 11,7% heavier than the controls and presented higher glycemia 13,1%, insulinemia 70% and corticosteronemia 92,6%. Conclusion: Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults.

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

BackgroundPostnatal 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.MethodsThe 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.ResultsThe 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.ConclusionsLow-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.

Acephate exposure during a perinatal life program to type 2 diabetes.

Acephate has been used extensively as an insecticide in agriculture. Its downstream sequelae are associated with hyperglycemia, lipid metabolism dysfunction, DNA damage, and cancer, which are rapidly growing epidemics and which lead to increased morbidity and mortality rates and soaring health-care costs. Developing interventions will require a comprehensive understanding of which excess insecticides during perinatal life can cause insulin resistance and type 2 diabetes. A Wistar rat animal model suggests that acephate exposure during pregnancy and lactation causes alterations in maternal glucose metabolism and programs the offspring to be susceptible to type 2 diabetes at adulthood. Therapeutic approaches based on preventive actions to food contaminated with insecticides during pregnancy and lactation could prevent new cases of type 2 diabetes.

Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition

Low intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively. Exercised mothers showed low mesenteric fat pad stores and fasting glucose and improved glucose-insulin tolerance, VO2max during lactation and sympathetic activity. Moreover, the breast milk contained elevated levels of insulin. In addition, SL of sedentary mothers presented metabolic dysfunction and glucose and insulin intolerance and were hyperglycemic and hyperinsulinemic in adulthood. SL of exercised mothers showed lower fat tissue accretion and improvements in glucose tolerance, insulin sensitivity, insulinemia and glycemia. The results suggest that maternal exercise during the perinatal period can have a possible reprogramming effect to prevent metabolic dysfunction in adult rat offspring exposed to early overnutrition, which may be associated with the improvement in maternal health caused by exercise.

Protein-restriction diet during the suckling phase programs rat metabolism against obesity and insulin resistance exacerbation induced by a high-fat diet in adulthood

Protein restriction during the suckling phase can malprogram rat offspring to a lean phenotype associated with metabolic dysfunctions later in life. We tested whether protein-caloric restriction during lactation can exacerbate the effect of a high-fat (HF) diet at adulthood. To test this hypothesis, we fed lactating Wistar dams with a low-protein (LP; 4% protein) diet during the first 2 weeks of lactation or a normal-protein (NP; 23% protein) diet throughout lactation. Rat offspring from NP and LP mothers received a normal-protein diet until 60 days old. At this time, a batch of animals from both groups was fed an HF (35% fat) diet, while another received an NF (7% fat) diet. Maternal protein-caloric restriction provoked lower body weight and fat pad stores, hypoinsulinemia, glucose intolerance, higher insulin sensitivity, reduced insulin secretion and altered autonomic nervous system (ANS) function in adult rat offspring. At 90 days old, NP rats fed an HF diet in adulthood displayed obesity, impaired glucose homeostasis and altered insulin secretion and ANS activity. Interestingly, the LP/HF group also presented fat pad and body weight gain, altered glucose homeostasis, hyperleptinemia and impaired insulin secretion but at a smaller magnitude than the NP-HF group. In addition, LP/HF rats displayed elevated insulin sensitivity. We concluded that protein-caloric restriction during the first 14 days of life programs the rat metabolism against obesity and insulin resistance exacerbation induced by an obesogenic HF diet.

Neonatal treatment with scopolamine butylbromide prevents metabolic dysfunction in male rats.

We tested whether treatment with a cholinergic antagonist could reduce insulin levels in early postnatal life and attenuate metabolic dysfunctions induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SLs, 3 pups/dam) and normal litters (NLs, 9 pups/dam) were used in models of early overfeeding and normal feeding, respectively. During the first 12 days of lactation, animals in the SL and NL groups received scopolamine butylbromide (B), while the controls received saline (S) injections. The drug treatment decreased insulin levels in pups from both groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, vagus nerve activity, fat tissue accretion, insulinemia, leptinemia, body weight gain and food intake. Low glucose and cholinergic insulinotropic effects were observed in pancreatic islets from both groups. Low protein expression was observed for the muscarinic M3 acetylcholine receptor subtype (M3mAChR), although M2mAChR subtype expression was increased in SL-B islets. In addition, beta-cell density was reduced in drug-treated rats. These results indicate that early postnatal scopolamine butylbromide treatment inhibits early overfeeding-induced metabolic dysfunctions in adult rats, which might be caused by insulin decreases during lactation, associated with reduced parasympathetic activity and expression of M3mAChR in pancreatic islets.

Maternal Diet Supplementation with n-6/n-3 Essential Fatty Acids in a 1.2 : 1.0 Ratio Attenuates Metabolic Dysfunction in MSG-Induced Obese Mice

Essential polyunsaturated fatty acids (PUFAs) prevent cardiometabolic diseases. We aimed to study whether a diet supplemented with a mixture of n-6/n-3 PUFAs, during perinatal life, attenuates outcomes of long-term metabolic dysfunction in prediabetic and obese mice. Seventy-day-old virgin female mice were mated. From the conception day, dams were fed a diet supplemented with sunflower oil and flaxseed powder (containing an n-6/n-3 PUFAs ratio of 1.2 : 1.0) throughout pregnancy and lactation, while control dams received a commercial diet. Newborn mice were treated with monosodium L-glutamate (MSG, 4 mg g−1 body weight per day) for the first 5 days of age. A batch of weaned pups was sacrificed to quantify the brain and pancreas total lipids; another batch were fed a commercial diet until 90 days of age, where glucose homeostasis and glucose-induced insulin secretion (GIIS) as well as retroperitoneal fat and Lee index were assessed. MSG-treated mice developed obesity, glucose intolerance, insulin resistance, pancreatic islet dysfunction, and higher fat stores. Maternal flaxseed diet-supplementation decreased n-6/n-3 PUFAs ratio in the brain and pancreas and blocked glucose intolerance, insulin resistance, GIIS impairment, and obesity development. The n-6/n-3 essential PUFAs in a ratio of 1.2 : 1.0 supplemented in maternal diet during pregnancy and lactation prevent metabolic dysfunction in MSG-obesity model.