Maternal high fat diet consumption reduces liver alpha7 nicotinic cholinergic receptor expression and impairs insulin signalling in the offspring

Autor(es)

Costa, S. O. ^[1] ; Souza, C. M. ^[1] ; Lanza, P. G. ^[1] ; Sartori, J. O. ^[1] ; Ignacio-Souza, L. M. ^{[1, 2]} ; Candreva, T. ^[3] ; Rodrigues, H. G. ^[3] ; Torsoni, A. S. ^{[1, 2]} ; Milanski, M. ^{[1, 2]} ; Torsoni, M. A. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Sch Appl Sci, Lab Metab Disorders, Campinas - Brazil

^[2] Univ Estadual Campinas, Obes & Comorbid Res Ctr, Campinas - Brazil

^[3] Univ Estadual Campinas, Sch Appl Sci, Lab Nutrients & Tissue Repair, Campinas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 JAN 8 2020.
• Citações Web of Science: 3

Resumo

The activation of nicotinic acetylcholine receptor alpha 7 subunit (alpha 7nAChR) has been associated to anti-inflammatory response in macrophages. High-fat diet (HFD) consumption during pregnancy and lactation impairs the cholinergic anti-inflammatory pathway in liver and white adipose tissue of offspring. In order to evaluate the relationship between damage in the cholinergic anti-inflammatory pathway and insulin resistance (IR) development, the liver of offspring of obese dams was investigated. Additionally, the capacity of alpha 7nAChR activation to reduce IR induced by saturated fatty acid was investigated in hepatoma cell line. Initially, female mice were subjected to either standard chow (SC) or HFD during pregnancy and lactation period. After weaning, only male offspring from HFD dams (HFD-O) and SC dams (SC-O) were fed with the SC diet. Hepatic alpha 7nAChR expression was downregulated, and hepatic TNF-alpha, IL-1 beta, and pIKK level, but not pJNK, were elevated in the HFD-O compared to SC-O mice. Besides, hepatic expression of TNF-alpha in response to lipopolysaccharide (LPS) was higher in HFD-O than SC-O mice. Insulin-stimulated phosphorylation of the AKT was lower in HFD-O compared to SC-O. Additionally, insulin-stimulated phosphorylation of the AKT in KO alpha 7(Alb-Cre) mice fed HFD was lower than WT mice fed HFD. In hepatoma cell line, palmitate increased IL-6 and TNF-alpha expressions and pJNK level. These effects were accompanied by reduced capacity of insulin to stimulate AKT phosphorylation. PNU or nicotine reduced cytokine expression and JNK activation, but improved insulin resistance induced by palmitate. Our results suggest that maternal obesity impairs hepatic alpha 7nAChR expression and AKT phosphorylation in the offspring. In vitro studies suggest that alpha 7nAChR activation has potential to reduce deleterious effect of saturated fatty acids on insulin signalling. (AU)

• Processo FAPESP: 16/23484-1 - Participação de receptores colinérgicos do tipo nicotínico alfa7 (alfa7nAChR) na prevenção do desenvolvimento de resistência à insulina
• Beneficiário: Marcio Alberto Torsoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs