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Evaluation of cholinergic anti-inflammatory pathway in the hypothalamus and white adipose tissue of offspring mice with obesity induced by maternal consumption of high fat diet

Grant number: 15/02741-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2015
Effective date (End): May 31, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Marcio Alberto Torsoni
Grantee:Camilla Mendes de Souza
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

The increase in obesity in the population has been followed by an increase in the prevalence of obesity in women of childbearing age. This has increased the interest in understanding the metabolic abnormalities in the offspring that would be caused by maternal obesity during pregnancy. Pregnancy and lactation are essential processes for phenotypic adaptations of offspring. Studies have shown that exposure to a high fat diet during this period has obesogenic effects on progeny promoting neuronal alterations that lead to increased dietary intake, impaired glucose tolerance and insulin resistance, changes in hepatic lipid metabolism in adult offspring, damage to the hypothalamic signaling and increased inflammatory intracellular signaling. The innate immune system is responsible for protect the body against infectious processes, has its intensity controlled by the cholinergic anti-inflammatory reflex. When acetylcholine binds to ±7 subunit of the nicotinic acetylcholine receptor (±7nAChR) activates a signaling cascade that promotes the reduction of the expression of pro-inflammatory cytokines. Changes in this pathway have been associated with obesity, inflammation, insulin resistance and animals that do not express ±7nAChR have abnormal inflammatory response and reduced sensitivity to insulin. On the other hand, the activation of this pathway by nicotine diminishes inflammation in adipose tissue and improves insulin sensitivity in obesity animal models. Our research hypothesis is that the offspring of obese mothers presents loss of cholinergic anti-inflammatory reflex and this is associated with metabolic damage and maternal obesity. To test this hypothesis the offspring (28 days) of mothers that consumed high-fat diet during pregnancy and lactation will be investigated in relation to the i- distribution of ±7nAChR the central nervous system, ii- hypothalamic and white adipose tissue activation of the signaling pathway proteins (JAK2 / STAT3) in the offspring of obese mothers and offspring control after pharmacological stimulation of ±7nAChR the central nervous system. For these analyzes will be used immunofluorescence and real-time PCR to analyze the expression and distribution of ±7nAChR in the hypothalamus and western blot to evaluate the phosphorylation of JAK2 / STAT3 protein in adipose tissue and hypothalamus after central administration of pharmacological activator ±7nAChR .