ABSTRACT
The Labrador Retriever is among the main breeds with the greatest predisposition to obesity. Several factors, especially the interrelationships between food management, exercise and social factors; influence the likelihood of a dog becoming obese. Furthermore, genetic factors are also responsible for obesity in dogs, and in Labrador Retriever, a frameshift mutation (P187fs) in pro-opiomelanocortin (POMC) gene is strongly associated with obesity. There is no knowledge of studies that have previously evaluated the prevalence of the canine POMC deletion (P187fs) in Brazilian Labrador Retriever. Therefore, the objective of this study was to investigate this mutation in Labrador Retriever dogs in Brazil. Of the 108 Labrador Retrievers that were assessed in this study, 59 were from a previous study, composed by animals assisted in a veterinary hospital with unknown lineage, and 49 were from a prospective study, composed of 19 pet and 30 assistance/rescue Labrador Retriever dogs. The obesity risk and appetite questionnaire were applied, with some modifications, to tutors of the animals used in the prospective study. Fragments of the DNA, containing the mutation, were amplified by PCR and submitted to direct gene sequencing. The allele frequency of the mutation was 21.3% and was out of Hardy-Weinberg equilibrium (P<0.05). Using only the data of animals with known lineage, the presence of the mutated allele was higher in the Assistance/rescue Group than Pet Group (P<0.01), furthermore, the allele frequencies observed in Assistance Group (31.7%) was out of Hardy-Weinberg equilibrium (P<0.05), while that in the Pet Group (18.4%) was in equilibrium (P>0.05). Although the mutation has increased the food-motivation in the assistance/rescue dogs, other variables, especially frequent exercising, favored that these animals maintained the ideal body weight (body condition score = 5). In summary, the Hardy-Weinberg disequilibrium observed in the allele distribution of the deletion POMC_P187fs in this study, independently of the Labrador Retriever group assessed, suggesting the possibility of positive selection of the mutated allele, which may lead to the maintenance of this deleterious allele in the studied population.(AU)
O Labrador Retriever é uma das principais raças caninas com maior predisposição à obesidade. Vários fatores, especialmente as interrelações entre a alimentação, exercício e fatores sociais, influenciam a probabilidade de um cão se tornar obeso. Além disso, fatores genéticos são também responsáveis pela obesidade em cães, e no Labrador Retriever a mutação "frameshift" P187fs no gene pró-opiomelanocortina (POMC) está fortemente associada à obesidade. Não existem estudos prévios de prevalência da deleção P187fs no gene POMC em cães Labrador Retriever no Brasil. Portanto, o objetivo deste estudo foi investigar esta mutação em cães da raça Labrador Retriever no Brasil. Dos 108 Labradores Retrievers avaliados neste estudo, 59 eram de um estudo retrospectivo (composto por animais atendido no hospital veterinário e sem linhagem conhecida) e 49 eram de um estudo prospectivo (composto por 19 cães pet e 30 cães de assistência/resgate). Um questionário de risco de obesidade modificado foi aplicado nos tutores dos animais usados no estudo prospectivo. Fragmentos de DNA, contendo a mutação, foram amplificados por PCR e submetidos ao sequenciamento gênico direto. A frequência alélica da mutação foi de 21,3% e estava fora do equilíbrio de Hardy-Weinberg (P<0,05). Usando somente os dados dos animais de linhagem conhecida, a presença do alelo mutado foi maior no Grupo de cães de Assistência/resgate que no Grupo de Pets (P<0,01), além disso, as frequências alélicas nos Grupos de Assistência/resgate (31,7%) e no de pets (18,4%) estavam fora e em equilíbrio de Hardy-Weinberg (P<0,05), respectivamente. Embora a mutação tenha aumentado a motivação pelo alimento em cães Labrador Retriever do Grupo de Assistência/resgate, outras variáveis, especialmente o frequente exercício, favoreceu a manutenção o peso corporal ideal (peso corporal = 5). Em resumo, o desequilíbrio de Hardy-Weinberg observado na distribuição do alelo POMC_P187fs observado neste estudo, independentemente do grupo de Labrador Retriever avaliado, sugere a possibilidade de uma seleção positiva para o alelo mutado, o qual poderá levar a manutenção desse alelo deletério nesta população.(AU)
Subject(s)
Animals , Male , Female , Dogs , Pro-Opiomelanocortin/genetics , Obesity/genetics , Obesity/veterinaryABSTRACT
OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of hypothalamic sirtuin 1(SIRT1) and proopiomelanocortin (POMC), and body weight, food-intake, blood glucose, and blood lipid levels in obese rats, so as to explore its mechanisms underlying improvement of obesity. METHODS: Forty male Wistar rats were randomly divided into normal, model, EA, and sham EA groups (n＝10 rats in each group). The obesity model was established by feeding the rats with high fat diet. EA (2 Hz, 1 mA) was applied to "Zusanli" (ST36), "Zhongwan" (CV12), "Guanyuan" (CV4) and "Fenglong" (ST40) or sham acupoints (about 5 mm beside each acupoint, shallow needling) for 20 min, once every other day for 8 weeks. The rats' body weight and food-intake were recorded. The blood glucose (fasting plasma glucose: FPG, postprandial plasma glucose: PPG) and blood lipids (triglyceride: TG, total cholesterol: TC, non esterified fatty acid: NEFA) were assayed by using an automatic biochemical analyzer. The protein and mRNA expression levels of SIRT1 and POMC in the hypothalamus were detected by Western blot and quantitative real-time PCR, respectively. RESULTS: In comparison with the normal group, the body weight, food-intake, blood lipids, and PPG levels were significantly increased (P<0.05，P<0.01), and the expression levels of SIRT1 protein and mRNA in the hypothalamus were significantly doun-regulated in the model group (P<0.05). Following EA, the body weight, food-intake, blood lipids, and PPG levels were considerably down-regulated (P<0.01，P<0.05), and the expression levels of SIRT1 and POMC protein and mRNA in the hypothalamus were significantly up-regulated in the EA group rather than those in the sham EA and the model groups (P<0.05)．. CONCLUSION: EA can reduce the obese rats' body weight, food-intake, blood lipids and blood glucose, which may be associated with its effect in up-regulating the SIRT1 and POMC expression of hypothalamus.
ABSTRACT
Reactive Oxygen Species (ROS) are not just by products of substrate oxidation but also chemicals that are involved in intracellular signaling when they are generated transiently and moderately. This review explores the intracellular signaling aspects of reactive oxygen species in influencing feeding behaviour. Substrates like glucose and lipids stimulate generation of reactive oxygen species mainly through mitochondria and to some extent through the NADPH oxidases. The level of ROS generated in hypothalamic neurons like NPY/AgRP and POMC neurons, under the influence of substrate level, directly influences the activity of these neurons and subsequently affect the downstream neurons located in other parts of the hypothalamus like the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the lateral hypothalamus. Activation of POMC neuronal population is driven by increase ROS level whereas activation of NPY/AgRP neurons occurs when ROS level is reduced. The activation of these neurons will determine the feeding behaviour which will either be satiety if POMC neurons are activated or increase food intake if NPY/AgRP neurons are activated.
ABSTRACT
OBJECTIVE: Capsaicin, a noxious stimulant and main component of the hot flavor of red peppers, has an analgesic effect when administered to humans. We investigated the expression of proopioimelanocortin (POMC) mRNA in the arcuate nucleus of Sprague-Dawley (SD) rats after administering capsaicin, hypothesizing that administering capsaicin activates the central opioid system. METHODS: SD rats were divided randomly into two groups; one group received a saline injection and the other received a capsaicin injection. The POMC mRNA level in the arcuate nucleus of the hypothalamus was measured by the reverse transcription-polymerase chain reaction at 0, 20, 40, 60, and 120 minutes after capsaicin administration. RESULTS: Capsaicin administration resulted in a significantly increased POMC mRNA level, compared to that in saline-treated rats at the 20-minute time point (t=-4.445, p=0.001). However, no significant group differences were observed at other times (t=-1.886, p=0.089; t= -0.973, p=0.353; t=-2.193, p=0.053 for 40, 60, and 120 minutes, respectively). CONCLUSION: The analgesic effect of capsaicin might be associated with increased activity of the cerebral opioid system. This finding suggests that capsaicin acted for nociception and analgesia and could affect alcohol-intake behavior, which might further imply that a food culture could affect drinking behavior.
Subject(s)
Animals , Humans , Rats , Analgesia , Arcuate Nucleus of Hypothalamus , beta-Endorphin , Capsaicin , Capsicum , Drinking Behavior , Hypothalamus , Nociception , Pro-Opiomelanocortin , Rats, Sprague-Dawley , RNA, MessengerABSTRACT
Pele sensível (PS) é definida como uma condição de tolerância reduzida ao uso freqüente ou prolongado de cosméticos e produtos de higiene pessoal, que apresenta desde sinais clínicos visíveis, como eritema, edema e descamação, até sinais neurossensoriais subjetivos de desconforto, como pinicamento, queimação, prurido, ressecamento e dor. A fisiopatologia da PS consiste em reação inflamatória decorrente de uma disfunção da barreira cutânea associada ao desequilíbrio da resposta neuroimunoendocrinológica da pele. Neste trabalho demonstramos os efeitos do produto Relievene® SK sobre a proteção do metabolismo celular, considerando as atividades adaptógena e neuroendócrina deste composto, bem como a melhora da função da barreira cutânea e da hiper-reatividade da pele em indivíduos com PS.
ABSTRACT
OBJECTIVE: Proopiomelanocortin (POMC) gene is involved in various neuroendocrine reproductive activities and its principal areas of expression are hypothalamus and pituitary gland. However, as it is known as low copy gene, detection of its expression by in situ hybridization is challenging. This study was to examine the degree of basal expression of POMC mRNA and anatomic localization of its expression in rat hypothalamus and pituitary gland as a preliminary study for related reproductive endocrine researches. METHODS: Hypothalamus and pituitary gland of ovariectomized female Spraque-Dawley rat (weight: 250-300 g) was obtained by decapitation with preservation of POMC mRNA by cardiac perfusion of 4% paraformaldehyde. Then, coronal sections of hypothalamus and horizontal sections of pituitary gland were made after paraffin embedding. For in situ hybridization, 35S-labeled antisense RNA probe was used and after in situ hybridization reaction and serial washing procedure, detection of its signal was made by emulsion autoradiography of slide and dark field microscopic examination was done for photographic documentation. Anatomic localization of various nucleus of hypothalamus was done by method proposed by Paxinos and Watson1. RESULTS: Strong expression signal of POMC mRNA was detected in the intermediate lobe of pituitary gland. Less strong, but evenly distributed signals were also detected in the anterior lobe of pituitary gland. In hypothalamic sections, entire area of arcuate nucleus from rostral to caudal direction (between bregma -2.80 mm to bregma -4.30 mm area) showed clear and strong signal of POMC mRNA expression. CONCLUSION: Though POMC gene is known as low copy gene, its basal mRNA expression in pituitary gland and hypothalamus in ovariectomized rat were detectable by in situ hybridization technique. As subpopulation of arcuate nucleus are under complex differential regulation, this in situ hybridization model would be helpful for understanding the effects of various regulatory factors on expression of POMC gene in the specific anatomic area of hypothalamus and pituitary gland.
Subject(s)
Animals , Female , Humans , Rats , Arcuate Nucleus of Hypothalamus , Autoradiography , Decapitation , Hypothalamus , In Situ Hybridization , Paraffin Embedding , Perfusion , Pituitary Gland , Pituitary Gland, Anterior , Pituitary Gland, Intermediate , Pro-Opiomelanocortin , RNA, Antisense , RNA, MessengerABSTRACT
The effect of hydrocortisone (135 nag i.v. as a bolus) on the levels of serum N-POMC was studied in the patients with Cushing's disease [including three groups: untreated (CD, n=8), post-adrenolectomy without Nelson's syndrome (CDA, n=5), and Nelson's syndrome (NS, n=4)]; Addison's disease (AD, n = 13) and congenital adrenal hyperplasia (CAH, n=4). The results showed that the levels of serum N-POMC were decreased after the administration of hydrocortisone in all three groups of Cushing's disease, however the suppression rate of N-POMC was much lower in these groups than that in AD and CAH (P