Epigenetic alterations of the alpha-7 nicotinic acetylcholine receptor (a7nAchR) in the gut-brain axis of offspring programmed by maternal obesity

• Grant number: 24/02099-9
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Agreement: CNPq
• 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 research grant: 23/02026-9 - 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, AP.R
• Associated scholarship(s): 24/15837-8 - Epigenetic alterations of alpha-7 nicotinic acetylcholine receptor (¿7nAchR) in the gut-brain axis of offspring programmed by maternal obesity, BP.JD

Abstract

Studies in the field of Developmental Origins of Health and Disease (DOHaD) have shown that the self-perpetuation of obesity is related to metabolic programming resulting from critical periods of development. Obesity is closely related to subclinical inflammation, and recent work from our group has demonstrated that exposure to an obesogenic diet promotes impairments in the anti-inflammatory response by reducing the expression and signaling of the alpha-7 nicotinic acetylcholine receptor (a7nAchR). It is known that the gastrointestinal tract (GIT) acts as a potential source of systemic inflammation through disruption of the microbiota and intestinal permeability, and that obesity and the consumption of obesogenic diets are major triggers of these disturbances. The network of innervations of the intestine that provides sensory information to the central nervous system (CNS) about the intestinal physiological state, known as the "gut-brain axis," is responsible for controlling a wide variety of physiological functions, including the secretion of neurotransmitters responsible for fine control of food intake and energy expenditure. Clinical studies have already demonstrated the relationship between maternal obesity with maternal dysbiosis and subclinical inflammation, and adverse outcomes in fetal or postnatal health, including impacts on neurodevelopment and increased risk of overweight and obesity. However, the role of inflammation control in the gut-brain axis in the development of hyperphagia and obesity in offspring of obese dams is not yet understood, and the molecular mechanisms involved in this scenario also require further investigation. Our hypothesis is that maternal obesity during gestation leads to a decrease in ±7nAchR expression in the gut-brain axis of the developing offspring through epigenetic mechanisms, leading to impairments in hypothalamic energy balance control. (AU)