RESUMEN
BACKGROUND: Adherence to low-carbohydrate, ketogenic diets (KDs) has been associated with greater weight loss in the short-term than low-fat, calorie-restricted diets. However, consumption of KDs may result in decreased voluntary exercise and thus render long-term weight loss and maintenance of weight loss difficult. METHODS: Rats were maintained on either a non-ketogenic chow (CH) diet or a low-carbohydrate, KD for 6 weeks. Half of each dietary group was sedentary, whereas the other half was given access to a running wheel. Running wheel activity (total distance and meters per minute), plasma leptin and insulin, adiposity, and hypothalamic mRNA for neuropeptide Y and proopiomelanocortin (POMC) were measured to assess activity-related effects in animals maintained on KD. RESULTS: With access to a running wheel, rats on KD engaged in similar levels of voluntary activity as CH rats and both dietary groups decreased caloric intake. Caloric intake increased over time such that it was significantly greater than sedentary controls after 1 month of access to the wheels, however body weight remained decreased. Sedentary rats maintained on KD had increased adiposity and plasma leptin levels and decreased hypothalamic POMC mRNA, as compared to sedentary CH rats. KD rats with access to a running wheel had similar levels of adiposity and plasma leptin levels as CH rats with access to running wheels, but significantly increased POMC mRNA in the arcuate. CONCLUSION: We demonstrate that maintenance on KD does not inhibit voluntary activity in a running wheel. Furthermore, prevention of KD-related increased adiposity and plasma leptin, as measured in sedentary KD rats, significantly increases levels of the anorexigenic neuropeptide POMC mRNA.
Asunto(s)
Adiposidad/fisiología , Peso Corporal/fisiología , Hipotálamo/fisiología , Leptina/sangre , Actividad Motora/fisiología , Animales , Dieta Baja en Carbohidratos , Dieta Cetogénica , Hipotálamo/metabolismo , Insulina/sangre , Masculino , Neuropéptido Y/sangre , Neuropéptido Y/genética , Condicionamiento Físico Animal , Proopiomelanocortina/sangre , Proopiomelanocortina/genética , ARN Mensajero/sangre , Ratas , Ratas Long-Evans , Transducción de Señal/fisiologíaRESUMEN
Much evidence suggests that the hypothalamic melanocortin (MC) system plays an important role in the control of food intake. However, investigations of the potential behavioral mechanisms have been limited to measures of aversion. The purpose of the present experiment was to assess whether other behavioral consequences of administration of MC peptides were similar to those produced by 0- or 24-h food deprivation, respectively. Rats were first trained while food deprived that a tone predicted the delivery of peanut oil. They then received exposure to oil under food deprivation, satiation, intra-third-cerebroventricular (i3vt) infusion of MTII (a potent MC agonist) or SHU-9119 (a potent MC antagonist). All rats were then tested during extinction for levels of responding to the tone under food satiation. Previous results demonstrated that sated exposure reduces subsequent test responding to the tone. During the present extinction test, rats that received sated exposure exhibited reduced responding to the tone, relative to rats that received deprived exposure. Unlike satiation, rats that received exposure after MTII exhibited continued high levels of responding to the tone. Further, rats that received SHU-9119 exhibited a small reduction in responding. These data suggest that MTII and SHU-9119 do not influence intake via the same mechanisms as hunger and food satiation, respectively.
Asunto(s)
Conducta Apetitiva/fisiología , Hipotálamo/fisiología , Receptores de Corticotropina/fisiología , Animales , Conducta Apetitiva/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Hipotálamo/efectos de los fármacos , Masculino , Hormonas Estimuladoras de los Melanocitos/farmacología , Oligopéptidos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Corticotropina/agonistas , Receptores de Corticotropina/antagonistas & inhibidores , Receptores de Melanocortina , Tercer Ventrículo/efectos de los fármacos , Tercer Ventrículo/fisiología , alfa-MSH/análogos & derivadosRESUMEN
Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced by neurons of the lateral hypothalamic area (LHA). Because genetic MCH deficiency induces hypophagia and loss of body fat, we hypothesized that MCH neurons may represent a specific LHA pathway that, when inhibited, contributes to the pathogenesis of certain anorexia syndromes. To test this hypothesis, we measured behavioral, hormonal, and hypothalamic neuropeptide responses in two models of hyperestrogenemia in male rats, a highly reproducible anorexia paradigm. Whereas estrogen-induced weight loss engaged multiple systems that normally favor recovery of lost weight, the expected increase of MCH mRNA expression induced by energy restriction was selectively and completely abolished. These findings identify MCH neurons as specific targets of estrogen action and suggest that inhibition of these neurons may contribute to the hypophagic effect of estrogen.