ABSTRACT
Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation - Control (C) and High-fat (H). Post-weaning Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life's day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.
A exposição à dieta hiperlipídica pode alterar o controle da ingestão de alimentos, promovendo hiperfagia e obesidade. O objetivo deste estudo foi investigar os efeitos dessa dieta sobre a expressão gênica dos receptores de dopamina (drd1 e drd2), da proopiomelanocortina (pomc) e neuropeptídeo Y (npy), e preferência alimentar em ratos adultos. Ratas Wistar foram alimentadas com uma dieta hiperlipídica ou controle durante a gestação e lactação. Os descendentes foram alocados em grupos: Lactação Controle (C) e Hiperlipídica (H). Pós-desmame - Controle Controle (CC), descendentes das genitoras do grupo controle e alimentados com dieta controle após o desmame; Controle Hiperlipídica (CH), descendentes das genitoras do grupo controle e alimentados com dieta hiperlipídica após o desmame; Hiperlipídica Controle (HC), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta controle após o desmame; Hiperlipídica Hiperlipídica (HH), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta hiperlipídica após o desmame. Os grupos CH e HH apresentaram maior expressão de drd1 em comparação ao CC. O drd2 de CH e HC apresentou maior expressão gênica que o CC. HH apresentou maior expressão de pomc em comparação com os outros grupos. O HC também apresentou maior expressão de pomc em comparação ao CH. O npy do HH apresentou maior expressão em relação ao CH e HC. HH e HC tiveram uma preferência maior por uma dieta rica em gordura no 102º dia de vida. A dieta hiperlipídica alterou a expressão gênica dos drd1, drd2, pomc e npy e influenciou na preferência alimentar pela dieta hiperlipídica.
Subject(s)
Animals , Female , Pregnancy , Rats , Pro-Opiomelanocortin/genetics , Diet, High-Fat/adverse effects , Body Weight , Neuropeptide Y/genetics , Gene Expression , Receptors, Dopamine/genetics , Rats, Wistar , Food PreferencesABSTRACT
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
Background: Melanocortinergic system represents a known system involved in the central regulation of body weight with the central proopiomelanocortin [POMC] neurons forming a potent anorexigenic network. Polymorphisms in the POMC gene locus are associated with obesity phenotypes
Aim: To assess the contribution of the POMC gene 9-bp insertional polymorphism in the susceptibility to obesity and its relation to body mass index [BMI] and adiposity-related co-morbidities in obese children and adolescents; as well as binge eating behavior
Patients and methods: Fifty obese children and adolescents with simple obesity were screened for Binge Eating Disorder [BED] by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5], they were compared to 50 age, sex and pubertal stage-matched non obese controls. Anthropometric measurements, blood pressure, abdominal ultrasound for fatty liver, measurement of fasting lipid profile, fasting insulin, fasting blood glucose and assessment of POMC gene 9-bp insertional polymorphism were done
Results: Obese patients had significantly higher anthropometric measurements, blood pressure percentiles, fasting glucose, fasting insulin, homeostasis model assessment for insulin resistance [HOMA-IR] and fasting lipid profiles, and higher frequency of occurrence of non alcoholic fatty liver disease and BED. Allelic frequencies of POMC gene 9 bp insertional polymorphism were comparable in patients and controls [p= 0.956]. Fasting insulin levels were significantly higher in the heterozygous cases having the polymorphism than in wild homozygous cases; whereas no difference was observed among the controls
Conclusion: This polymorphism was associated with higher fasting insulin levels in the obese patients only. These findings support the hypothesis that the melanocortin pathway may modulate glucose metabolism in obese subjects indicating a possible gene-environment interaction. POMC variant may be involved in the natural history of polygenic obesity, contributing to the link between type 2 diabetes and obesity