Avaliação da termogênese e inflamação hipotalâmica em modelos de programação para obesidade

Abstract

Both maternal smoking and early weaning are insults that cause the development of obesity and endocrine-metabolic changes in adult offspring. Several changes occur in the hypothalamus and brown adipose tissue (BAT) in response to obesity. Thus, we investigated the long-term repercussions of maternal smoking and early weaning on the BAT thermogenic capacity and the hypothalamus funtion. Model of neonatal exposure to cigarette smoke during lactation: lactating Wistar rats with their pups were separated into 2 groups: SMOKE (exposure to cigarette 3R4F / 4x / 1 h, from PN3-PN21) and CONTROL (exposure to filtered air). The offspring were euthanized in PN180. Direct and indirect exposure to cigarette smoke during lactation reduced the thermogenic capacity of TAM in the offspring from both sexes as well as altered the hypothalamic circuitry favoring hyperphagia. However, only the males showed inflammation in the hypothalamus. Model of exclusive maternal exposure to nicotine during lactation: In PN3, mini-pumps were implanted in lactating rats, which were divided into 2 groups: NICOTINE (6 mg / kg BW / day, for 14 days) and CONTROL (saline). The offspring were euthanized in PN120 and PN180. We evidence that postnatal exposure to nicotine compromised the function of TAM and white adipose tissue in both sexes, contributing to the susceptibility and / maintenance of obesity in male offspring. Early weaning (EW) model: lactating rats were randomly separated into 3 groups: NON-PHARMACOLOGICAL EW: mothers were wrapped with an adhesive bandage in the last 3 days of lactation; PHARMACOLOGICAL EW: mothers were treated with bromocriptine to block milk production (1mg / kg BW / day) in the last 3 days of lactation; CONTROL: pups were freely breastfed and weaned in the standard period (21 days of life). The animals were euthanized in PN180. Early weaning altered the thermogenic capacity of BAT, partially contributing to obesity in adulthood, despite differences related to the type of weaning. In summary, we show that the programmed obesity phenotype is related to BAT dysfunction and that there are important sex-related differences in the models studied.