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1.
Mol Cell Endocrinol ; 586: 112203, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490633

RESUMO

Microcystin (MC) is most common cyanobacterial toxin. Few studies have evaluated the MC effects on the hypothalamic-pituitary-gonadal (HPG) axis and metabolic function. In this study, we assessed whether MC exposure results in HPG axis and metabolic changes. Female rats were exposed to a single dose of MC at environmentally relevant levels (5, 20 and 40 µg/kg). After 24 h, we evaluated reproductive and metabolic parameters for 15 days. MC reduced the hypothalamic GnRH protein expression, increased the pituitary protein expression of GnRHr and IL-6. MC reduced LH levels and increased FSH levels. MC reduced the primary follicles, increased the corpora lutea, elevated levels of anti-Müllerian hormone (AMH) and progesterone, and decreased estrogen levels. MC increased ovarian VEGFr, LHr, AMH, ED1, IL-6 and Gp91-phox protein expression. MC increased uterine area and reduced endometrial gland number. A blunted estrogen-negative feedback was observed in MC rats after ovariectomy, with no changes in LH levels compared to intact MC rats. Therefore, these data suggest that a MC leads to abnormal HPG axis function in female rats.


Assuntos
Eixo Hipotalâmico-Hipofisário-Gonadal , Microcistinas , Ratos , Feminino , Animais , Microcistinas/toxicidade , Interleucina-6/metabolismo , Ovário/metabolismo , Estrogênios , Hormônio Liberador de Gonadotropina/metabolismo
2.
Reprod Toxicol ; 119: 108410, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37211340

RESUMO

We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHß+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHß+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.


Assuntos
Hipotálamo , Obesidade , Ratos , Feminino , Animais , Hipotálamo/metabolismo , Obesidade/metabolismo , Núcleo Arqueado do Hipotálamo/metabolismo , Dieta , Carboidratos , Kisspeptinas/genética , Kisspeptinas/metabolismo
3.
Life Sci ; 307: 120873, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35952730

RESUMO

AIMS: Perinatal maternal hypercaloric diets increase the susceptibility to metabolic disorders in the offspring. We hypothesized that maternal intake of an isocaloric moderate-fat diet (mMFD) would disturb the glucose homeostasis and favor the ß-cell failure in response to fructose overload in adult male offspring. METHODS: Female Wistar rats received an isocaloric diet (3.9 kcal/g) containing 29 % (mMFD) or 9 % as fat (mSTD) prior mating and throughout gestation and lactation. After weaning, male offspring received standard chow and fructose-drinking water (15 %) between 120 and 150 days old. KEY FINDINGS: mMFD offspring had higher body weight, visceral adiposity and, fasting glycemia, with normal insulinemia. Fructose increased glycemia at 15 min from oral glucose administration, but only mMFD had returned to basal glucose levels at 120 min. Fructose increased HOMA-IR index regardless diet, but only mMFD exhibited hyperinsulinemia and a higher HOMA-ß index. mMFD pancreatic islets showed increased area and insulin immunostaining density, suggesting ß-cell hypertrophy. Fructose induced the expected compensatory hypertrophy in mSTD islets, while the opposite occurred in mMFD islets, associated with reduced insulin immunostaining, suggesting lower insulin storage. Pancreatic islets isolated from mMFD offspring exhibited higher glucose-stimulated insulin release at physiological concentrations. However, at higher glucose concentrations, the islets from fructose-treated mMFD reduced dramatically their insulin release, suggesting exhaustion. SIGNIFICANCE: Isocaloric mMFD induced adaptive mechanism in the offspring allowing insulin hypersecretion, but under metabolic challenge with fructose, ß-cell compensation shifts to exhaustion, favoring dysfunction. Therefore, a maternal MFD may contribute to developing diabetes under fructose overload in the adult offspring.


Assuntos
Água Potável , Ilhotas Pancreáticas , Efeitos Tardios da Exposição Pré-Natal , Animais , Glicemia/metabolismo , Dieta , Dieta Hiperlipídica , Feminino , Frutose/efeitos adversos , Glucose , Humanos , Hipertrofia , Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos , Ratos Wistar
4.
J Dev Orig Health Dis ; 13(6): 800-805, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35241213

RESUMO

The COVID-19 pandemic has exposed several inequalities worldwide, including the populations' access to healthcare systems and economic differences that impact the access to vaccination, medical resources, and health care services. Scientific research activities were not an exception, such that scientific research was profoundly impacted globally. Research trainees and early career researchers (ECRs) are the life force of scientific discovery around the world, and their work and progress in research was dramatically affected by the COVID-19 pandemic. ECRs are a particularly vulnerable group as they are in a formative stage of their scientific careers, any disruptions during which is going to likely impact their lifelong career trajectory. To understand how COVID-19 impacted lives, career development plans, and research of Developmental Origins of Health and Disease (DOHaD) ECRs, the International DOHaD ECR committee formed a special interest group comprising of ECR representatives of International DOHaD affiliated Societies/Chapters from around the world (Australia and New Zealand, Canada, French Speaking DOHaD, Japan, Latin America, Pakistan and USA). The anecdotal evidence summarized in this brief report, provide an overview of the findings of this special interest group, specifically on the impact of the evolving COVID-19 pandemic on daily research activities and its effects on career development plans of ECRs. We also discuss how our learnings from these shared experiences can strengthen collaborative work for the current and future generation of scientists.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Atenção à Saúde , Paquistão , Pandemias , Pesquisadores
5.
Mol Nutr Food Res ; 66(8): e2100514, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35175665

RESUMO

SCOPE: Perinatal maternal obesity and excessive fructose consumption have been associated with liver metabolic diseases. The study investigates whether moderate maternal high-fat diet affects the liver mitochondria responses to fructose intake in adult offspring. METHODS AND RESULTS: Wistar female rats have received a standard diet (mSTD) or high-fat diet (mHFD) (9% and 28.6% fat, respectively), before mating until the end of lactation. Male offspring were fed standard diet from weaning to adulthood and received water or fructose-drinking water (15%) from 120 to 150 days old. Fructose induces liver mitochondrial ultrastructural alterations with higher intensity in mHFD offspring, accompanied by reduced autophagy markers. Isolated mitochondria respirometry shows unaltered ATP-coupled oxygen consumption with increased Atp5f1b mRNA only in mHFD offspring. Fructose increases basal respiration and encoding complex I-III mRNA, only in mSTD offspring. Uncoupled respiration is lower in mHFD mitochondria that are unable to exhibit fructose-induced increase Ucp2 mRNA. Fructose decreases antioxidative defense markers, increases unfolded protein response and insulin resistance only in mHFD offspring without fructose-induced hepatic lipid accumulation. CONCLUSION: Mitochondrial dysfunction and homeostatic disturbances in response to fructose are early events evidencing the higher risk of fructose damage in the liver of adult offspring from dams fed an isocaloric moderate high-fat diet.


Assuntos
Dieta Hiperlipídica , Efeitos Tardios da Exposição Pré-Natal , Adulto , Filhos Adultos , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Frutose/efeitos adversos , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Mitocôndrias Hepáticas/metabolismo , Gravidez , RNA Mensageiro , Ratos , Ratos Wistar
6.
J Dev Orig Health Dis ; 13(2): 252-262, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33818369

RESUMO

Nicotine is the main psychoactive substance present in cigarette smoke that is transferred to the baby by breast milk. In rats, maternal nicotine exposure during breastfeeding induces obesogenesis and hormone dysfunctions in adult male offspring. As glucocorticoid (GC), insulin, and vitamin D change both adipogenesis and lipogenesis processes, we assessed parameters related to metabolism and action of these hormones in visceral and subcutaneous adipose tissues (VAT and SAT) of adult male and female rats in a model of neonatal nicotine exposure. At postnatal (PN) day 2, dams were kept with six pups (three per sex) and divided into nicotine and control groups for implantation of osmotic minipumps that released 6 mg/kg nicotine or saline, respectively. At PN180, fat mass, hormone levels, and protein contents of biomarkers of the GC activation and receptor (11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor alpha), insulin signaling pathway [insulin receptor beta (IRß), phosphorylated insulin receptor substrate 1, insulin receptor substrate 1 (IRS1), phosphorylated serine/threonine kinase (pAKT), serine/threonine kinase, glucose transporter type 4 (GLUT4)], and vitamin D activation and receptor (1α-hydroxylase and vitamin D receptor) were evaluated. While nicotine-exposed males showed increased fat mass, hypercorticosteronemia, hyperinsulinemia, and higher 25-hydroxyvitamin D, these alterations were not observed in nicotine-exposed females. Nicotine-exposed males only showed lower IRS1 in VAT, while the females had hyperglycemia, higher pAKT in VAT, while lower IRß, IRS1, and GLUT4 in SAT. Parameters related to metabolism and action of GC and vitamin D were unaltered in both sexes. We evidence that exposure exclusively to nicotine during breastfeeding affects the hormone status and fat depots of the adult progeny in a sex-dependent manner.


Assuntos
Insulina , Nicotina , Animais , Feminino , Glucocorticoides , Humanos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Nicotina/efeitos adversos , Proteínas Serina-Treonina Quinases , Ratos , Ratos Wistar , Serina , Vitamina D
7.
Neuropharmacology ; 200: 108821, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610290

RESUMO

The breastfeeding period is one of the most important critical windows in our development, since milk, our first food after birth, contains several compounds, such as macronutrients, micronutrients, antibodies, growth factors and hormones that benefit human health. Indeed, nutritional, and environmental alterations during lactation, change the composition of breast milk and induce alterations in the child's development, such as obesity, leading to the metabolic dysfunctions, cardiovascular diseases and neurobehavioral disorders. This review is based on experimental animal models, most of them in rodents, and summarizes the impact of an adequate breast milk supply in view of the developmental origins of health and disease (DOHaD) concept, which has been proposed by researchers in the areas of epidemiology and basic science from around the world. Here, experimental advances in understanding the programming during breastfeeding were compiled with the purpose of generating knowledge about the genesis of chronic noncommunicable diseases and to guide the development of public policies to deal with and prevent the problems arising from this phenomenon. This review article is part of the special issue on "Cross talk between periphery and brain".


Assuntos
Aleitamento Materno , Desenvolvimento Infantil/fisiologia , Nível de Saúde , Leite Humano/química , Doenças não Transmissíveis/epidemiologia , Adolescente , Animais , Criança , Pré-Escolar , Doença Crônica , Humanos , Lactente , Fórmulas Infantis/química , Recém-Nascido , Leite/química , Leite/imunologia , Leite Humano/imunologia
8.
Food Chem Toxicol ; 144: 111623, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32738371

RESUMO

Metabolic syndrome (MetS) is characterized by increased abdominal fat, dyslipidemia, diabetes mellitus and hypertension. A high MetS prevalence is strongly associated with obesity. Obesity is a public health problem in which several complex factors have been implicated, including environmental pollutants. For instance, maternal smoking seems to play a role in obesogenesis in childhood. Given the association between endocrine disruptors, obesity and metabolic programming, over the past 10 years, our research group has contributed to studies based on the hypothesis that early exposure to nicotine/tobacco causes offspring to become MetS-prone. The mechanism by which tobacco smoking during breastfeeding induces metabolic dysfunctions is not completely understood; however, increased metabolic programming has been shown in studies that focus on this topic. Here, we reviewed the literature mainly based in light of our latest data from experimental models. Nicotine or tobacco exposure during breastfeeding induces several endocrine dysfunctions in a sex- and tissue-specific manner. This review provides an updated summary regarding the hypothesis that early exposure to nicotine/tobacco causes offspring to become MetS-prone. An understanding of this issue can provide support to prevent long-term disorders, mainly related to the risk of obesity and its comorbidities, in future generations.


Assuntos
Aleitamento Materno , Fumar Cigarros , Síndrome Metabólica/etiologia , Modelos Biológicos , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Síndrome Metabólica/induzido quimicamente , Obesidade/metabolismo , Gravidez , Fatores de Risco
9.
Mol Nutr Food Res ; 64(3): e1900838, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31916388

RESUMO

SCOPE: Non-alcoholic fatty liver disease (NAFLD) among adolescents has been related to fructose intake. Additionally, maternal high-fat diet (mHFD) increases the offspring susceptibility to NAFLD at adulthood. Here, it is hypothesized that mHFD may exacerbate the fructose impact in adolescent male rat offspring, by changing the response of contributing mechanisms to liver injury. METHODS AND RESULTS: Female Wistar rats receive standard (mSTD: 9% fat) or high-fat diet (mHFD: 29% fat) prior mating throughout pregnancy and lactation. After weaning, offspring receive standard chow and, from the 25th to 45th day, receive water or fructose-drinking water (15%). At 46 days old, fructose groups show increased adiposity, increased serum and hepatic triglycerides, regardless of maternal diet. Fructose aggravates the hepatic imbalance of redox state already exhibited by mHFD offspring. The hepatic activation of cellular repair pathways by fructose, such as unfolded protein response and macroautophagy, is disrupted only in mHFD offspring. Fructose does not change the liver morphology of mSTD offspring. However, it intensifies the liver injury already present in mHFD offspring. CONCLUSION: Fructose intake during adolescence accelerates the emergence of NAFLD observed previously at the adult life of mHFD offspring, and reveals a differentiated hepatic response to metabolic insult, depending on the maternal diet.


Assuntos
Dieta Hiperlipídica , Frutose/toxicidade , Hepatopatia Gordurosa não Alcoólica/etiologia , Envelhecimento , Animais , Autofagia , Peso Corporal , Suscetibilidade a Doenças , Estresse do Retículo Endoplasmático , Feminino , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo , Gravidez , Ratos Wistar , Triglicerídeos/sangue , Resposta a Proteínas não Dobradas
10.
Mol Cell Endocrinol ; 462(Pt B): 119-126, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28962894

RESUMO

Obesity is associated with an imbalance in the activity of the autonomic nervous system (ANS), specifically in the organs involved in energy metabolism. The pancreatic islets are richly innervated by the ANS, which tunes the insulin release due to changes in energy demand. Therefore, changes in the sympathetic input that reach the pancreas can lead to metabolic dysfunctions. To evaluate the role of the sympathetic ends that innervate the pancreas, 60-day-old male Wistar rats were subjected to sympathectomy (SYM) or were sham-operated (SO). At 120 day-old SYM rats exhibited an increase in body weight, fat pads and metabolic dysfunctions. Decreases in the HOMA-IR and reductions in insulin release were observed both in vivo and in vitro. Furthermore, the SYM rats exhibited altered pancreatic islet function in both muscarinic and adrenergic assays and exhibited high protein expression of the alpha-2 adrenergic receptor (α2AR). Because α2AR has been linked to type 2 diabetes, these findings demonstrate the clinical implications of this study.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Homeostase , Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Sistema Nervoso Simpático/metabolismo , Envelhecimento , Animais , Células Cultivadas , Resistência à Insulina , Ilhotas Pancreáticas/citologia , Masculino , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa 2/metabolismo
11.
Endocrine ; 56(2): 346-356, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28233096

RESUMO

BACKGROUND/AIMS: Autonomic nervous system imbalance is associated with metabolic diseases, including diabetes. Glibenclamide is an antidiabetic drug that acts by stimulating insulin secretion from pancreatic beta cells and is widely used in the treatment of type 2 diabetes. Since there is scarce data concerning autonomic nervous system activity and diabetes, the aim of this work was to test whether glibenclamide can improve autonomic nervous system activity and muscarinic acetylcholine receptor function in pre-diabetic obese male rats. METHODS: Pre-diabetes was induced by treatment with monosodium L-glutamate in neonatal rats. The monosodium L-glutamate group was treated with glibenclamide (2 mg/kg body weight /day) from weaning to 100 days of age, and the control group was treated with water. Body weight, food intake, Lee index, fasting glucose, insulin levels, homeostasis model assessment of insulin resistance, omeostasis model assessment of ß-cell function, and fat tissue accumulation were measured. The vagus and sympathetic nerve electrical activity were recorded. Insulin secretion was measured in isolated islets challenged with glucose, acetylcholine, and the selective muscarinic acetylcholine receptor antagonists by radioimmunoassay technique. RESULTS: Glibenclamide treatment prevented the onset of obesity and diminished the retroperitoneal (18%) and epididymal (25%) fat pad tissues. In addition, the glibenclamide treatment also reduced the parasympathetic activity by 28% and glycemia by 20% in monosodium L-glutamate-treated rats. The insulinotropic effect and unaltered cholinergic actions in islets from monosodium L-glutamate groups were increased. CONCLUSION: Early glibenclamide treatment prevents monosodium L-glutamate-induced obesity onset by balancing autonomic nervous system activity.


Assuntos
Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Obesidade/metabolismo , Estado Pré-Diabético/tratamento farmacológico , Nervo Vago/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/metabolismo , Sistema Nervoso Autônomo/fisiopatologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Insulina/sangue , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Obesidade/fisiopatologia , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/fisiopatologia , Ratos , Ratos Wistar , Glutamato de Sódio , Nervo Vago/fisiopatologia
12.
J Endocrinol ; 230(1): 27-38, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27113853

RESUMO

Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic ß-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Insulina/metabolismo , Obesidade/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Nervo Vago/fisiopatologia , Animais , Glucose/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Obesidade/induzido quimicamente , Obesidade/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Wistar , Glutamato de Sódio , Nervo Vago/metabolismo
13.
Cancer Biol Ther ; 16(6): 958-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26024008

RESUMO

It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Metformina/farmacologia , Neoplasias/patologia , Animais , Antineoplásicos/administração & dosagem , Modelos Animais de Doenças , Feminino , Xenoenxertos , Masculino , Metformina/administração & dosagem , Neoplasias/tratamento farmacológico , Ratos
14.
Exp Physiol ; 100(1): 57-68, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25398717

RESUMO

NEW FINDINGS: What is the central question of this study? Different nerve 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. Obesity has become a global problem, and this condition develops primarily because of an imbalance between energy intake and expenditure. The high complexity involved in the regulation of energy metabolism results from several factors besides endocrine factors. It has been suggested that obesity could be caused by an imbalance in the autonomous nervous system, which could lead to a condition of high parasympathetic activity in counterpart to low sympathetic tonus. High-fat (HF) diets have been used to induce obesity in experimental animals, and their use in animals leads to insulin resistance, hyperinsulinaemia and high parasympathetic activity, among other disorders. The aim of this work was to evaluate the effects of a vagotomy performed at the initiation of a HF diet at two different stages of life, weaning and adulthood. The vagotomy reduced parasympathetic activity (-32 and -51% in normal fat-fed rats and -43 and -55% in HF diet-fed rats; P < 0.05) and fat depots (-17 and -33%, only in HF diet-fed rats; P < 0.05). High-fat diet-fed rats exhibited fasting hyperinsulinaemia (fivefold higher in young rats and threefold higher in older rats; P < 0.05); however, vagotomy corrected it in younger rats only, and a similar effect was also observed during the glucose tolerance test. The insulin resistance exhibited by the HF diet-fed groups was not altered in the vagotomized rats. We suggest that the vagus nerve, in addition to the important role of parasympathetic activity, contributes to the condition of obesity, and that non-vagal pathways may be involved along with the imbalanced autonomic nervous system.


Assuntos
Dieta Hiperlipídica , Síndrome Metabólica/etiologia , Obesidade/etiologia , Nervo Vago/fisiopatologia , Adiposidade , Fatores Etários , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Modelos Animais de Doenças , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/prevenção & controle , Obesidade/sangue , Obesidade/fisiopatologia , Obesidade/prevenção & controle , Ratos Wistar , Fatores de Tempo , Vagotomia , Nervo Vago/cirurgia , Desmame , Aumento de Peso
15.
Cell Physiol Biochem ; 33(4): 1075-86, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24732778

RESUMO

BACKGROUND/AIMS: Impaired pancreatic beta cell function and insulin secretion/action are a link between obesity and type 2 diabetes, which are worldwide public health burdens. We aimed to characterize the muscarinic acetylcholine receptor (mAChR) M1-M4 subtypes in isolated pancreatic islets from pre-diabetic obese rats that had been treated neonatally with monosodium L-glutamate (MSG). METHODS: At 90 days of age, both the MSG and the control groups underwent biometric and biochemical evaluation. Anti-muscarinic drugs were used to study mAChR function either in vivo or in vitro. RESULTS: The results demonstrated that atropine treatment reduced insulin secretion in the MSG-treated and control groups, whereas treatment with an M2mAChR-selective antagonist increased secretion. Moreover, the insulinostatic effect of an M3mAChR-selective antagonist was significantly higher in the MSG-treated group. M1mAChR and M3mAChR expression was increased in the MSG-obese group by 55% and 73%, respectively. In contrast, M2mAChR expression decreased by 25% in the MSG group, whereas M4mAChR expression was unchanged. CONCLUSIONS: Functional changes in and altered content of the mAChR (M1-M4) subtypes are pivotal to the demand for high pancreatic beta cell insulin secretion in MSG-obese rats, which is directly associated with vagal hyperactivity and peripheral insulin resistance.


Assuntos
Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Obesidade/metabolismo , Receptores Muscarínicos/metabolismo , Glutamato de Sódio/farmacologia , Animais , Glicemia/análise , Teste de Tolerância a Glucose , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Obesidade/patologia , Ratos , Ratos Wistar , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M2/metabolismo , Receptor Muscarínico M3/metabolismo , Receptor Muscarínico M4/metabolismo , Receptores Muscarínicos/química
16.
Br J Nutr ; 111(2): 227-35, 2014 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-23841989

RESUMO

Impaired pancreatic ß-cell function, as observed in the cases of early nutrition disturbance, is a major hallmark of metabolic diseases arising in adulthood. In the present study, we aimed to investigate the function/composition of the muscarinic acetylcholine receptor (mAChR) subtypes, M2 and M3, in the pancreatic islets of adult offspring of rats that were protein malnourished during lactation. Neonates were nursed by mothers that were fed either a low-protein (4 %, LP) or a normal-protein (23 %, NP) diet. Adult rats were pre-treated with anti-muscarinic drugs and subjected to the glucose tolerance test; the function and protein expression levels of M2mAChR and M3mAChR were determined. The LP rats were lean and hypoinsulinaemic. The selective M2mAChR antagonist methoctramine increased insulinaemia by 31 % in the NP rats and 155 % in the LP rats, and insulin secretion was increased by 32 % in the islets of the NP rats and 88 % in those of the LP rats. The selective M3mAChR antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide decreased insulinaemia by 63 % in the NP rats and 40 % in the LP rats and reduced insulin release by 41 % in the islets of the NP rats and 28 % in those of the LP rats. The protein expression levels of M2mAChR and M3mAChR were 57 % higher and 53 % lower, respectively, in the islets of the LP rats than in those of the NP rats. The expression and functional compositions of M2mAChR and M3mAChR were altered in the islets of the LP rats, as a result of metabolic programming caused by the protein-restricted diet, which might be another possible effect involved in the weak insulin secretion ability of the islets of the programmed adult rats.


Assuntos
Ração Animal/análise , Proteínas Alimentares/administração & dosagem , Células Secretoras de Insulina/fisiologia , Lactação/fisiologia , Receptores Muscarínicos/classificação , Receptores Muscarínicos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Glicemia , Dieta/veterinária , Feminino , Glucose/metabolismo , Intolerância à Glucose , Teste de Tolerância a Glucose , Homeostase , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Antagonistas Muscarínicos/farmacologia , Gravidez , Ratos , Ratos Wistar
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