Effect of palmitate treatment on the expression of genes involved in the regulation of proopiomelanocortina

• Grant number: 21/10279-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2021
• Effective date (End): June 30, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Guilherme Barros de Mattos
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity is defined as an abnormal accumulation of adipose tissue capable of causing damage to the individual's health, being considered a worldwide public health problem. The regulation of food intake and energy expenditure occur through the action of populations of neurons located in the hypothalamic arcuate nucleus, one of these populations expressing the precursor of the neurotransmitter proopiomelanocortin (POMC). Such neurons are activated by the action of insulin and leptin and exert anorexigenic signals, decreasing food intake and increasing energy expenditure. POMC is a neurotransmitter precursor that needs to be processed by a series of protein convertases to produce active neuropeptides such as alpha-MSH and beta-endorphin.Clinical and experimental studies have revealed that disturbances in the expression and processing of POMC result in increased food intake and subsequently obesity. Among these disorders are changes in the levels of convertases Pc1/3, Pc2, Prcp and Cpe, which cleave specific regions of this neuropeptide forming smaller derivatives, among them the melanocyte-alpha stimulating hormone (±-MSH), responsible for stimulating the second-order neurons located in the paraventricular nucleus (PVN).Under physiological conditions, this neural network guarantees the stability of body mass over time. However, several factors can alter this circuit, leading to anabolism and a progressive increase in adiposity. Some factors that cause this phenomenon are the increased consumption of ultra-processed foods, rich in fats and simple sugars.Palmitate is a saturated fatty acid found abundantly in processed foods and most animal foods. Its excessive intake results in alterations in this neuronal circuit, which can lead to an imbalance in energy metabolism, due, in large part, to the beginning of an inflammatory process in the hypothalamus. Recently, studies by our group described that palmitate can alter the function of protein convertases and, consequently, impair the cleavage process of the neuropeptide POMC (RAZOLLI; DE ARAÚJO; SANT APOS ANA; KIRWAN et al., 2020).The aim of this study is to evaluate the effect of palmitate on the expression of convertases in hypothalamic neuron strains. For this purpose, the cell lines will be treated for different times, 1, 4 or 8 hours, with different concentrations of palmitate and the expression of transcripts encoding POMC will be evaluated by real-time PCR. In addition, POMC, alpha-MSH and beta-endorphin by-products will be evaluated by ELISA.The results of this study should contribute to advance the characterization of the mechanisms involved in disorders of the functional regulation of POMC neurons in obesity. (AU)