Fecal Microbiota Transplantation During Lactation Programs the Metabolism of Adult Wistar Rats in a Sex-specific Way.

BACKGROUND: The intestinal microbiota is involved in many physiological processes. However, the effects of microbiota in metabolic programming still unknow. We evaluated whether the transplantation of fecal microbiota during early life can program health or disease during adulthood in a model of lean and obese male and female Wistar rats. METHODS: Parental obesity were induced using a small litter (SL, 3 pups/dam) model. At 90 d old, normal litter (NL, 9 pups/dam) and SL males and females (parents) from different litters were mated: NL male vs. NL female; SL male vs. SL female. After birth, male and female offspring rats were also standardized in normal litters or small litters . From the 10th until 25th d of life, the NL and SL male and female offspring received via gavage of a solution containing the diluted feces of the opposite dam (fecal microbiota, M) or saline solution (S). At 90 d of age, biometric and biochemical parameters were assessed. RESULTS: NLM male rats transplanted with obese microbiota showed increased body weight, and fat pad deposition, hyperinsulinemia, glucose intolerance and dyslipidemia. SLM male rats transplanted with lean microbiota had decreased retroperitoneal and mesenteric fat, triglycerides and VLDL levels and improvement of glucose tolerance. Despite SLM female rats showed higher visceral fat, microbiota transplantation in female rats caused no changes in these parameters compared with control groups. CONCLUSION: Fecal microbiota transplantation during lactation induces long-term effects on the metabolism of male Wistar rats. However, female rats were resistant to metabolic alterations caused by the treatment.

Lean in one way, in obesity another: effects of moderate exercise in brown adipose tissue of early overfed male Wistar rats.

BACKGROUND: Early postnatal overfeeding (PO) induces long-term overweight and reduces brown adipose tissue (BAT) thermogenesis. Exercise has been suggested as a possible intervention to increase BAT function. In this study, we investigated chronical effects of moderate-intensity exercise in BAT function in postnatal overfed male Wistar rats METHODS: Litters' delivery was on postnatal-day 0 - PN0. At PN2, litters were adjusted to nine (normal litter - NL) or three pups (small litter - SL) per dam. Animals were weaned on PN21 and in PN30 randomly divided into sedentary (NL-Sed and SL-Sed) or exercised (NL-Exe and SL-Exe), N of 14 litters per group. Exercise protocol started (PN30) with an effort test; training sessions were performed three times weekly at 60% of the VO2max achieved in effort test, until PN80. On PN81, a temperature transponder was implanted beneath the interscapular BAT, whose temperature was assessed in periods of lights-on and -off from PN87 to PN90. Sympathetic nerve activation of BAT was registered at PN90. Animals were euthanized at PN91 and tissues collected RESULTS: PO impaired BAT thermogenesis in lights-on (pPO < 0.0001) and -off (pPO < 0.01). Exercise increased BAT temperature in lights-on (pExe < 0.0001). In NL-Exe, increased BAT activity was associated with higher sympathetic activity (pExe < 0.05), ß3-AR (pExe < 0.001), and UCP1 (pExe < 0.001) content. In SL-Exe, increasing BAT thermogenesis is driven by a combination of tissue morphology remodeling (pExe < 0.0001) with greater effect in increasing UCP1 (pExe < 0.001) and increased ß3-AR (pExe < 0.001) content. CONCLUSION: Moderate exercise chronically increased BAT thermogenesis in both, NL and SL groups. In NL-Exe by increasing Sympathetic activity, and in SL-Exe by a combination of increased ß3-AR and UCP1 content with morphologic remodeling of BAT. Chronically increasing BAT thermogenesis in obese subjects may lead to higher overall energy expenditure, favoring the reduction of obesity and related comorbidities.

Early postnatal overnutrition impairs VO2max gains with moderate exercise and increase post-exercise muscle damage in adult male rats.

Exercise counteracts obesity effects, but information on how early-life obesity may affect long-term adaptation to exercise is lacking. This study investigates the impact of early-life postnatal overfeeding (PO) on animals' adaptation to exercise. Only male Wistar rats were used. On postnatal day (PN) 30, rats from control (NL-9 pups) or PO (SL-3 pups) litters were separated into four groups: NL-sedentary (NL-Se), NL-exercised (NL-Ex), SL-sedentary (SL-Se), and SL-exercised (SL-Ex). Exercised groups performed moderate-intensity exercise, running on a treadmill, from PN30 to PN90. Further experiments were carried out between PN90 and PN92. PO promoted obesity in SL versus NL rats (P < 0.05). Exercise reduced body weight (P < 0.001), body fat (P < 0.01), and improved glucose homeostasis in SL-Ex versus SL-Se. SL-Ex presented lower VO2max (P < 0.01) and higher post-exercise LDH (P < 0.05) compared to NL-Ex rats. Although moderate exercise counteracted obesity in SL rats, early-life overnutrition restricts fitness gains in adulthood, indicating that early obesity may impair animals' adaptation to exercise.

Soy isoflavones recover pancreatic islet function and prevent metabolic dysfunction in male rats.

We tested whether chronic supplementation with soy isoflavones could modulate insulin secretion levels and subsequent recovery of pancreatic islet function as well as prevent metabolic dysfunction induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SL, three pups/dam) and normal litters (NL, nine pups/dam) were used as models of early overfeeding and normal feeding, respectively. At 30 to 90 days old, animals in the SL and NL groups received either soy isoflavones extract (ISO) or water (W) gavage serving as controls. At 90 days old, body weight, visceral fat deposits, glycemia, insulinemia were evaluated. Glucose-insulin homeostasis and pancreatic-islet insulinotropic response were also determined. The early life overnutrition induced by small litter displayed metabolic dysfunction, glucose, and insulin homeostasis disruption in adult rats. However, adult SL rats treated with soy isoflavones showed improvement in glucose tolerance, insulin sensitivity, insulinemia, fat tissue accretion, and body weight gain, compared with the SL-W group. Pancreatic-islet response to cholinergic, adrenergic, and glucose stimuli was improved in both isoflavone-treated groups. In addition, different isoflavone concentrations increased glucose-stimulated insulin secretion in islets of all groups with higher magnitude in both NL and SL isoflavone-treated groups. These results indicate that long-term treatment with soy isoflavones inhibits early overfeeding-induced metabolic dysfunction in adult rats and modulated the process of insulin secretion in pancreatic islets.

Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats.

Metformin is an antidiabetic drug used for the treatment of diabetes and metabolic diseases. Imbalance in the autonomic nervous system (ANS) is associated with metabolic diseases. This study aimed to test whether metformin could improve ANS function in obese rats. Obesity was induced by neonatal treatment with monosodium L-glutamate (MSG). During 21-100 days of age, MSG-rats were treated with metformin 250 mg/kg body weight/day or saline solution. Rats were euthanized to evaluate biometric and biochemical parameters. ANS electrical activity was recorded and analyzed. Metformin normalized the hypervagal response in MSG-rats. Glucose-stimulated insulin secretion in isolated pancreatic islets increased in MSG-rats, while the cholinergic response decreased. Metformin treatment normalized the cholinergic response, which involved mostly the M3 muscarinic acetylcholine receptor (M3 mAChR) in pancreatic beta-cells. Protein expression of M3 mAChRs increased in MSG-obesity rats, while metformin treatment decreased the protein expression by 25%. In conclusion, chronic metformin treatment was effective in normalizing ANS activity and alleviating obesity in MSG-rats.

Malnutrition during late pregnancy exacerbates high-fat-diet-induced metabolic dysfunction associated with lower sympathetic nerve tonus in adult rat offspring.

Objectives: We aimed to assess the effects of a maternal protein-caloric restriction diet during late pregnancy on the metabolism of rat offspring fed a high-fat diet (HFD) during adulthood.Methods: During late pregnancy, rat dams received either a low-protein (4%; LP group) or normoprotein (23%; NP group) diet. After weaning, the offspring were fed a standard diet (Control; C). Male offspring (60 days old) from both groups were then fed either the C diet or HFD until they were 90 days old. The adult offspring and maternal metabolic parameters and autonomic nervous system (ANS) were then evaluated.Results: Dams exhibited low body weight gain and food intake during the LP diet consumption. At lactation, these dams showed high body weight gain, hypoinsulinemia and hyperglycemia. The maternal LP diet resulted in low body weights for the pups. There were also no differences in the metabolic parameters between the adult LP offspring that were fed the C diet and the NP group. Adults of both groups that were fed the HFD developed obesity associated with altered insulin/ glucose homeostasis and altered ANS activity; however, the magnitudes of these parameters were higher in the LP group than in the NP group.Conclusions: Maternal protein malnutrition during the last third of pregnancy malprograms the metabolism of rat offspring, resulting in increased vulnerability to HFD-induced obesity, and the correlated metabolic impairment might be associated with lower sympathetic nerve activity in adulthood.

Potential attenuation of early-life overfeeding-induced metabolic dysfunction by chronic maternal acetylcholinesterase inhibitor exposure.

Evidence suggests that low concentration perinatal exposure to environmental contaminants, such as organophosphate (OP) is associated with later life insulin resistance and type 2 diabetes. The aim of this work was to investigate whether chronic maternal OP exposure exacerbates metabolic dysfunctions in early-overfed rats. During pregnancy and lactational periods, dams received OP by gavage. To induce neonatal overnutrition at postnatal day 3, pups were standardized to 9 or 3 per nest. At 90-days-old, glucose-insulin homeostasis and insulin release from pancreatic islets were analyzed. While both OP exposure and overfeeding alone did induce diabetogenic phenotypes in adulthood, there was no exacerbation in rats that experienced both. Unexpectedly, the group that experienced both had improved adiposity, metabolic parameters, attenuated insulin release from isolated islets in the presence of glucose and low function of muscarinic acetylcholine receptor M3, as well as an attenuation of beta cell mass hyperplasia. High levels of butyrylcholinesterase and low levels of insulin in milk may contribute to the OP-induced developmental programming. Our study showed that maternal OP exposure may program insulin release as well as endocrine pancreas structure, thus affecting metabolism in adulthood. Our data suggest that while perinatal OP exposure alone increases the risk for later life T2D, it actually reverses many of the programmed metabolic dysfunction that is induced by postnatal overfeeding. These surprising results may suggest that low-dose administration of acetylcholinesterase inhibitors could be of utility in preventing detrimental developmental programming that is caused by early-life overnutrition.

Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats.

KEY POINTS: Cancer growth, cell proliferation and cachexia index can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins in adolescence. Walker 256 tumour-bearing rats who started exercise training during adolescence did not revert the basal low glycaemia and insulinaemia observed before tumour cell inoculation. The moderate exercise training improved glucose tolerance and peripheral insulin sensitivity only in rats exercised early in adolescence. The chronic effects of our exercise protocol are be beneficial to prevent cancer cachexia and hold clear potential as a nonpharmacological therapy of insulin sensitization. ABSTRACT: We tested the hypothesis that moderate exercise training, performed early, starting during adolescence or later in life during adulthood, can inhibit tumour cell growth as a result of changes in biometric and metabolic markers. Male rats that were 30 and 70 days old performed a treadmill running protocol over 8 weeks for 3 days week-1 , 44 min day-1 and at 55-65% V̇O2max . After the end of training, a batch of rats was inoculated with Walker 256 carcinoma cells. At 15 days after carcinoma cell inoculation, the tumour was weighed and certain metabolic parameters were evaluated. The data demonstrated that physical performance was better in rats that started exercise training during adolescence according to the final workload and V̇O2max . Early or later moderate exercise training decreased the cachexia index, cell proliferation and tumour growth; however, the effects were more pronounced in rats that exercised during adolescence. Low glycaemia, insulinaemia and tissue insulin sensitivity was not reverted in Walker 256 tumour-bearing rats who trained during adolescence. Cancer growth can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins during adolescence. In addition, improvement in glucose-insulin homeostasis might be involved in this process.

Moderate Physical Training Ameliorates Cardiovascular Dysfunction Induced by High Fat Diet After Cessation of Training in Adult Rats.

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.

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats.

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55-65% VO2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training did not cause injury or trigger inflammatory processes prior to tumor cell inoculation. Taken together, the current study suggests that aerobic exercise training applied during adolescence may mitigate tumor growth and related disorders in Walker 256 tumor-bearing adult rats. Improved insulin sensibility, lower glucose and insulin levels and/or reduced insulin secretion stimulated by glucose may be implicated in this tumor attenuation.

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.

Methylglyoxal treatment in lactating mothers leads to type 2 diabetes phenotype in male rat offspring at adulthood.

PURPOSE: Environmental and nutritional disorders during perinatal period cause metabolic dysfunction in the progeny and impair human health. Advanced glycation end products (AGEs) are primarily produced during metabolism of excess blood glucose, which is observed in diabetes. Methylglyoxal (MG) is a precursor for the generation of endogenous AGEs, which disturbs the metabolism. This work aimed to investigate whether the maternal MG treatment during lactation programs the progeny to metabolic dysfunction later in life. METHODS: Female Wistar rats were divided into two groups: control group (C) treated with saline and MG group treated with MG (60 mg/kg/day) by gavage throughout the lactation period. Both mothers and offspring were fed a standard chow. At weaning, breast milk composition was analyzed and mothers euthanized for blood and tissue sample collections. At 90 days of age, offspring were submitted to glucose tolerance test (ivGTT) and euthanized for blood and tissue samples collection. RESULTS: MG mothers showed increase in glucose and fructosamine levels; however, they showed low insulin levels and failure in ß-cell function (p < 0.05). MG mothers also showed dyslipidemia (p < 0.05). Moreover, breast milk had elevated levels of glucose, triglycerides, cholesterol and fructosamine and low insulin (p < 0.05). Interestingly, MG offspring had increased body weight and adipose tissue at adulthood, and they also showed glucose intolerance and failure in ß-cell function (p < 0.05). Besides, MG offspring showed dyslipidemia (p < 0.05) increasing cardiovascular diseases risk. CONCLUSIONS: Maternal MG treatment negatively affects the male rat offspring, leading to type 2 diabetes and dyslipidemia in later life, possibly by changes in breast milk composition.

Treatment with soy isoflavones during early adulthood improves metabolism in early postnatally overfed rats.

PURPOSE: The incidences of obesity and related diseases have reached epidemic proportions, and new therapeutic approaches are needed. Soy isoflavones have been identified as an important dietary factor for preventing and treating metabolic dysfunction. This study examined the effects of high doses of isoflavone on glucose and fat metabolism in a model of programmed obesity and evaluated its effects on the autonomic nervous system. METHODS: Litters of Wistar rats were standardized at nine pups per dam in normal litters (NL) or reduced to three pups per dam at the third day of life (P3) in small litters (SL) to induce postnatal overfeeding. Gavage with a soy bean isoflavone mixture (1 g/day) diluted in water was started at P60 and continued for 30 days. The control animals received vehicle gavage. At P90, biometric and metabolic parameters as well as direct autonomic nerve activity were measured. RESULTS: Increases in glycaemia and insulinaemia observed in SL rats were reduced by isoflavone treatment, which also caused lower glucose-induced insulin secretion by pancreatic islets. Sympathetic activity in the major splanchnic nerve was increased, while vagus nerve activity was reduced by isoflavone treatment. The dyslipidaemia induced by overfeeding in SL rats was restored by isoflavone treatment. CONCLUSION: The present study shows that treatment with isoflavone reduces adiposity and improves glucose and lipid metabolism. Collectively, these effects may depend on autonomic changes.

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.

Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats.

BACKGROUND/AIMS: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear. The aim of the present work was to evaluate whether obese adult rats that were chronically treated with an antidiabetic drug, glibenclamide, exhibit resistance to rodent breast carcinoma growth. METHODS: Neonatal rats were treated with monosodium L-glutamate (MSG) to induce prediabetes. Control and MSG groups were treated with Gli (2 mg/kg body weight/day) from weaning to 100 days old. After Gli treatment, the control and MSG rats were grafted with Walker-256 tumour cells. After 14 days, grafted rats were euthanized, and tumour weight as well as glucose homeostasis were evaluated. RESULTS: Treatment with Gli normalized tissue insulin sensitivity and glucose tolerance, suppressed fasting hyperinsulinaemia, reduced fat tissue accretion in MSG rats, and attenuated tumour growth by 27% in control and MSG rats. CONCLUSIONS: Gli treatment also resulted in a large reduction in the number of PCNA-positive tumour cells. Although treatment did improve the metabolism of pre-diabetic MSG-rats, tumour growth inhibition may be a more direct effect of glibenclamide.

Cross-fostering reduces obesity induced by early exposure to monosodium glutamate in male rats.

Maternal obesity programmes a range of metabolic disturbances for the offspring later in life. Moreover, environmental changes during the suckling period can influence offspring development. Because both periods significantly affect long-term metabolism, we aimed to study whether cross-fostering during the lactation period was sufficient to rescue a programmed obese phenotype in offspring induced by maternal obesity following monosodium L-glutamate (MSG) treatment. Obesity was induced in female Wistar rats by administering subcutaneous MSG (4 mg/g body weight) for the first 5 days of postnatal life. Control and obese female rats were mated in adulthood. The resultant pups were divided into control second generation (F2) (CTLF2), MSG-treated second generation (F2) (MSGF2), which suckled from their CTL and MSG biological dams, respectively, or CTLF2-CR, control offspring suckled by MSG dams and MSGF2-CR, MSG offspring suckled by CTL dams. At 120 days of age, fat tissue accumulation, lipid profile, hypothalamic leptin signalling, glucose tolerance, glucose-induced, and adrenergic inhibition of insulin secretion in isolated pancreatic islets were analysed. Maternal MSG-induced obesity led to an obese phenotype in male offspring, characterized by hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, dyslipidaemia, and impaired leptin signalling, suggesting central leptin resistance, glucose intolerance, impaired glucose-stimulated, and adrenergic inhibition of insulin secretion. Cross-fostering normalized body weight, food intake, leptin signalling, lipid profiles, and insulinaemia, but not glucose homeostasis or insulin secretion from isolated pancreatic islets. Our findings suggest that alterations during the lactation period can mitigate the development of obesity and prevent the programming of adult diseases.

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.

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.

Protein-energy malnutrition at mid-adulthood does not imprint long-term metabolic consequences in male rats.

PURPOSE: The long-term effects of the development of chronic metabolic diseases such as type 2 diabetes and obesity have been associated with nutritional insults in critical life stages. In this study, we evaluated the effect of a low-protein diet on metabolism in mid-adulthood male rats. METHODS: At 90 days of age, Wistar male rats were fed a low-protein diet (4.0 %, LP group) for 30 days, whereas control rats were fed a normal-protein diet (20.5 %, NP group) throughout their lifetimes. To allow for dietary rehabilitation, from 120 to 180 days of age, the LP rats were fed a normal-protein diet. Then, we measured body composition, fat stores, glucose-insulin homeostasis and pancreatic islet function. RESULTS: At 120 days of age, just after low-protein diet treatment, the LP rats displayed a strong lean phenotype, hypoinsulinemia, as assessed under fasting and glucose tolerance test conditions, as well as weak pancreatic islet insulinotropic response to glucose and acetylcholine (p < 0.01). At 180 days of age, after poor-protein diet rehabilitation, the LP rats displayed a slight lean phenotype (p < 0.05), which was associated with a high body weight gain (p < 0.001). Additionally, fat pad accumulation, glycemia and insulinemia, as well as the pancreatic islet insulinotropic response, were not significantly different between the LP and NP rats (p > 0.05). CONCLUSIONS: Taken together, the present data suggest that the effects of dietary restriction as a stressor in adulthood are reversible with dietary rehabilitation, indicating that adulthood is not a sensitive or critical time window for metabolic programming.

Short-term moderate exercise provides long-lasting protective effects against metabolic dysfunction in rats fed a high-fat diet.

INTRODUCTION: A sedentary lifestyle and high-fat feeding are risk factors for cardiometabolic disorders. This study determined whether moderate exercise training prevents the cardiometabolic changes induced by a high-fat diet (HFD). MATERIALS AND METHODS: Sixty-day-old rats were subjected to moderate exercise three times a week for 30 days. After that, trained rats received a HFD (EXE-HFD) or a commercial normal diet (EXE-NFD) for 30 more days. Sedentary animals also received the diets (SED-HFD and SED-NFD). Food intake and body weight were measured weekly. After 120 days of life, analyses were performed. Data were analysed with two-way ANOVA and the Tukey post-test. RESULTS: Body weight gain induced by HFD was attenuated in trained animals. HFD reduced food intake by approximately 30% and increased body fat stores by approximately 75%. Exercise attenuated 80% of the increase in fat pads and increased 24% of soleus muscle mass in NFD animals. HFD induced a hyper-response to glucose injection, and exercise attenuated this response by 50%. Blood pressure was increased by HFD, and the beneficial effect of exercise in reducing blood pressure was inhibited by HFD. HFD increased vagal activity by 65% in SED-HFD compared with SED-NFD rats, and exercise blocked this increase. HFD reduced sympathetic activity and inhibited the beneficial effect of exercise on ameliorating sympathetic activity. CONCLUSION: Four weeks of moderate exercise at low frequency was able to prevent the metabolic changes induced by a HFD but not the deleterious effects of diet on the cardiovascular system.