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

• Published in: Scientific reports Vol. 10; no. 1; p. 48
• Main Authors: Costa, S. O., Souza, C. M., Lanza, P. G., Sartori, J. O., Ignacio-Souza, L. M., Candreva, T., Rodrigues, H. G., Torsoni, A. S., Milanski, M., Torsoni, M. A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-01-2020; Nature Publishing Group
• Subjects: 13/106; 38/77; 631/443/319/1557; 692/163/2743/137/773; 692/163/2743/393; 96/1; 96/21; 96/95; Acetylcholine receptors; Adipose tissue; AKT protein; alpha7 Nicotinic Acetylcholine Receptor - metabolism; Animals; Animals, Newborn; Breastfeeding & lactation; Cytokines - metabolism; Diet; Diet, High-Fat - adverse effects; Down-Regulation; Fatty acids; Female; Hepatoma; High fat diet; Humanities and Social Sciences; Hypoglycemic Agents - pharmacology; IL-1β; Inflammation; Insulin; Insulin - pharmacology; Insulin Resistance; Interleukin 6; Kinases; Lactation; Lipopolysaccharides; Liver; Liver - drug effects; Liver - pathology; Macrophages; Male; Mice; multidisciplinary; Nicotine; Obesity; Obesity - etiology; Obesity - physiopathology; Offspring; Palmitic acid; Phosphorylation; Pregnancy; Proto-Oncogene Proteins c-akt - metabolism; Science; Science (multidisciplinary); Signal Transduction; Tumor necrosis factor-α; Weaning
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-56880-3

The activation of nicotinic acetylcholine receptor α7 subunit (α7nAChR) 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 α7nAChR 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 α7nAChR expression was downregulated, and hepatic TNF-α, IL-1β, and pIKK level, but not pJNK, were elevated in the HFD-O compared to SC-O mice. Besides, hepatic expression of TNF-α 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 KOα7
Alb-Cre
mice fed HFD was lower than WT mice fed HFD. In hepatoma cell line, palmitate increased IL-6 and TNF-α 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 α7nAChR expression and AKT phosphorylation in the offspring.
In vitro
studies suggest that α7nAChR activation has potential to reduce deleterious effect of saturated fatty acids on insulin signalling.