Maternal consumption of high fat diet and modulation of cholinergic anti-inflammatory pathway in offspring of mice

• Grant number: 14/18165-9
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2015
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Marcio Alberto Torsoni
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

The innate immune system is a major component of the barrier body's defense against infections. The defense reaction needs to be regulated to prevent cell damage and restore homeostasis. This occurs through the rapid, reversible and integrated anti-inflammatory response in the nervous system, called as the cholinergic anti-inflammatory reflex. This neural network is responsible for converting signals from the brain to the spleen, in an ±7 subunit of nicotinic acetylcholine receptor (±7nAChR) dependent manner. When acetylcholine interacts with ±7nAChR a cascade of proteins signaling is activated resulting in the inhibition of NFkB, thus decreasing the synthesis and release of proinflammatory cytokines. This pathway has been associated to reduced inflammation in pathologies such as Alzheimer's disease, Crohn's disease, rheumatoid arthritis, and experimental colitis. In obese individuals the expression of ±7nAChR is decreased in adipose tissue and the activation of the cholinergic anti-inflammatory pathway in mice improves insulin resistance and obesity-induced inflammation. Additionally the offspring of obese mothers has enhanced inflammatory response after LPS challenge. Therefore, our hypothesis is that maternal obesity may promote the failure of fine-tuning of the inflammatory response exerted by the cholinergic anti-inflammatory reflex. This change in signaling could contribute to activation of inflammatory pathways that promote cellular damage associated with obesity. To test this hypothesis the offspring (28 days) from dam with obesity induced by HFD during pregnancy and lactation will be investigated. The expression of ±7nAChR and components of cholinergic anti-inflammatory, activation of the inflammatory response and the recruitment and infiltration of macrophages will be examined in tissues such as the spleen, hypothalamus, liver and white adipose. Then, to evaluate the effects of heightened response in the contribution of metabolic damage associated with obesity, these animals will be challenged in adulthood by molecules that activate the pro-inflammatory response. The role of maternal supplementation with a mixture of type omega-3 fatty acids, which are associated with anti-inflammatory effects, will be also investigated to evaluate the effect of the supplementation in preventing damage related maternal obesity. (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)

DE PAULA SIMINO, LAIS ANGELICA; DE FANTE, THAIS; FONTANA, MARINA FIGUEIREDO; BORGES, FERNANDA OLIVEIRA; TORSONI, MARCIO ALBERTO; MILANSKI, MARCIANE; VELLOSO, LICIO AUGUSTO; TORSONI, ADRIANA SOUZA. Lipid overload during gestation and lactation can independently alter lipid homeostasis in offspring and promote metabolic impairment after new challenge to high-fat diet. NUTRITION & METABOLISM, v. 14, FEB 20 2017. (11/22156-7, 13/07607-8, 14/18165-9)

PAYOLLA, TANYARA BALIANI; LEMES, SIMONE FERREIRA; DE FANTE, THAIS; REGINATO, ANDRESSA; DA SILVA, CRISTIANO MENDES; MICHELETTI, THAYANA DE OLIVEIRA; RODRIGUES, HOSANA GOMES; TORSONI, ADRIANA SOUZA; MILANSKI, MARCIANE; TORSONI, MARCIO ALBERTO. High-fat diet during pregnancy and lactation impairs the cholinergic anti-inflammatory pathway in the liver and white adipose tissue of mouse offspring. Molecular and Cellular Endocrinology, v. 422, n. C, p. 192-202, FEB 15 2016. (13/10706-8, 14/18165-9)