Implications of maternal consumption of a high-fat diet on intestinal permeability modulation in developmental offspring: the participation of the alpha-7 nicotinic acetylcholine receptor

• Grant number: 23/02026-9
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Adriana Souza Torsoni
• Grantee: Adriana Souza Torsoni
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Marcio Alberto Torsoni
• Associated research grant(s): 24/02099-9 - Epigenetic alterations of the alpha-7 nicotinic acetylcholine receptor (a7nAchR) in the gut-brain axis of offspring programmed by maternal obesity, AP.R

Abstract

In both human and animal organisms, tissues can be individually programmed in critical periods of development, such as intrauterine life, in order to modulate their response to different environments after birth. Such modulation, in the long term, can lead to the development of diseases such as obesity and metabolic syndrome. In the US and Brazil, obesity and the metabolic syndrome are ongoing epidemics, posing major public health challenges and significant economic burdens. Adaptations in the microbiota and intestinal integrity have been highlighted in recent years in studies on human obesity, but little is known about the cause and effect relationships of these adaptations. An important issue in this field of science is whether the presence of inflammation associated with weight gain or the increase in levels of lipid mediators per se, prior to weight gain, would be responsible for establishing the pathophysiological mechanisms of this disease. Studies of the mechanisms involved in changes in intestinal permeability in individuals exposed to increased circulating lipids are still scarce, specifically in very short windows of development, such as the embryonic or infant stages. For this reason, the present project aims to evaluate whether maternal consumption of a high-fat diet during critical stages of development, such as pregnancy and lactation, leads to changes in the permeability and integrity of the intestinal epithelium barrier in the offspring, contributing to the development of obesity of the descendants. Furthermore, it is also our objective to investigate whether alterations in the anti-inflammatory reflex, through modulation of the alpha-7 nicotinic acetylcholine receptor, could be a mechanism involved in this process. Our expectation is that the results of this investigation will contribute to advances in knowledge and, consequently, in the control of the generational cycle of obesity, through more assertive therapeutic interventions, which promote reductions in public health expenditures. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BAQUEIRO, MAYARA DA NOBREGA; SIMINO, LAIS ANGELICA DE PAULA; COSTA, JOAO PAULO; PANZARIN, CAROLINA; REGINATO, ANDRESSA; TORSONI, MARCIO ALBERTO; IGNACIO-SOUZA, LETICIA; MILANSKI, MARCIANE; ROSS, MICHAEL G.; COCA, KELLY PEREIRA; et al. Sex-Dependent Variations in Hypothalamic Fatty Acid Profile and Neuropeptides in Offspring Exposed to Maternal Obesity and High-Fat Diet. NUTRIENTS, v. 16, n. 3, p. 22-pg., 2024-02-01. (23/02026-9)