Modulation of cholinergic anti-inflammatory pathway in the liver and white adipose tissue of the offspring by maternal high fat diet consumption

Author(s)

Tanyara Baliani Payolla

• Document type: Master's Dissertation
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2015-08-17

Examining board members

Marcio Alberto Torsoni; Rodrigo Ferreira de Moura; Augusto Ducati Luchessi

• Advisor: Marciane Milanski; Marcio Alberto Torsoni

Abstract

Maternal obesity is related to the development of metabolic disorders in offspring. The inflammatory process triggered by maternal consumption of high-fat diet appears to be triggered by activation of the TLR4/NFkB. The cholinergic anti-inflammatory reflex is activated by the vagus nerve and by the ?7 subunit of the nicotinic acetylcholine receptors (?7nAChR) reduces the activation of NF-kB and consequently decreases the production of TNF? and intensity of the immune response. Blockade of these receptors or efferent causes denervation of intense production of cytokines in response to lipopolysaccharide (LPS). In this regard, studies on experimental models have shown that obese offspring of mothers shows the increased inflammatory response following a challenge with LPS or (HFD). Thus, it is possible that these animals have control of fine-tuning the inflammatory response affected by HFD maternal consumption. The main objective was to evaluate the cholinergic anti-inflammatory pathway functionality (AIC) in the offspring of obese mothers. For this offspring of swiss males with 28 days old mice (d28) obtained from mothers fed with HFD diet (HFD-O) or control diet (SC-O) during pregnancy and lactation were used in the study. The LPS and nicotine were administered intraperitoneally (IP) and intracerebroventricular (i.c.v), respectively, and the track activity was evaluated. The results show repression in key protein involved in the cholinergic anti-inflammatory pathway in the liver and white adipose tissue (WAT), high serum levels of TNF-? and reducing markers M2 type macrophage (Chil 3, Arg1 e IL10) in the group HFD-O. The ?7nAChR was detected in immune system cells (co-located with F4/80) and adipocytes of group SC-O, not being obeserved receptor expression in adipocytes of HFD-O group. Furthermore, it was observed reduced association between STAT3 and NFkB in group HFD-O in both tissues after nicotine stimulation, basal activity greater acetylcholinesterase in the HFD-O and increased expression of TNF-? and IL-1? in liver and WAT of mice after stimulation with LPS, being this effect even greater in HFD-O. So we can conclude that maternal obesity and the consumption of HFD during pregnancy and lactation promotes molecular adaptations towards cholinergic pathway and these can lead to metabolic disorders associated with overnutrition in the perinatal period (AU)

• FAPESP's process: 13/10706-8 - Modulation of anti-inflammatory cholinergic pathway in the liver of the offspring by maternal consumption of high-fat diet
• Grantee: Tanyara Baliani Payolla
• Support Opportunities: Scholarships in Brazil - Master