Mecanismos centrais de regulação da ingestão alimentar no modelo de programação pela suplementação com óleo de coco em ratos adultos

Abstract

Metabolic Programming is a phenomenon, in which insults at critical stages of development, such as gestation and lactation, can lead to future metabolic dysfunction. Some oils, considered healthy, have been commonly used, even at critical windows of development. Recently, we observed that maternal exposure to coconut oil programs offspring for overweight and hyperphagia. We studied the effects of maternal supplementation with coconut oil during lactation, as well as the impact of continued exposure of this oil in the chow throughout life, on weight gain, adiposity and feeding behavior of the adult offspring. At birth, the pups were divided into two groups: 1) Soybean oil (SO); and 2) Coconut oil (CO). The dams of each group received the oils by gavage (0.5g / kg body mass) during lactation. Half of the CO group continued to receive coconut oil in the chow throughout life (CO+C). In PN180, both CO and CO+C groups had overweight, but only CO group had hyperfagia, higher visceral fat mass (VFM), hyperleptinemia and increased leptin content in VFM, while CO+C group had hypofagia, lower VFM and normoleptinemia compared to SO group. When we offered palatable diets (hyperlipidic and hyperglycidic) for 30 minutes and 12 hours, all groups ate more the hyperlipidic diet. However, the CO+C group had a significantly increased preference, characterizing greater voracity in this group compared to the other groups. We observed no change in the leptin receptor and its classical signaling pathway (Jak2-Stat3) in the arcuate hypothalamic nucleus (ARC), but the CO and CO+C groups had lower SOCS3 content. Only the CO+C group had lower content of GLP1R in the ARC, and the OC group showed higher content of DAGLα (enzyme of endocannabinoid synthesis) in the lateral hypothalamic nucleus, with no alteration of CB1r and FAAH (enzyme of endocannabinoid degradation). Maternal exposure to coconut oil programmed for hyperphagia, overweight and hyperleptinemia in adulthood, suggesting the development of resistance to the anorexigenic leptin effect. The classical leptin signaling pathway and the receptor of GLP1 in the ARC were normal in the CO group and did not explain the observed phenotype. The higher food intake in these animals can be explained by the greater expression of DAGLα, suggesting a greater synthesis of 2-AG, a known orexigenic mediator. Continuous exposure to coconut oil prevented most of the observed dysfunctions. Surprisingly, the CO+C group, although hypophagic, presented greater voracity when exposed to a hyperlipidic diet. A possible explanation for this finding is the lower content of the GLP1 receptor in the ARC, since this peptide inhibits short-term food intake.