title: Cardiotrophin-1 (CT-1) improves high fat diet-induced cognitive deficits in mice.
abstract: Previous studies demonstrated that a high fat diet (HFD) results in a loss of working memory in mice correlated with neuroinflammatory changes as well as synaptodendritic abnormalities and brain insulin resistance. Cardiotrophin-1 (CT-1), a member of the gp130 cytokine family, has been shown to potentially play a critical role in obesity and the metabolic syndrome. Our recent studies have demonstrated that CT-1 attenuates cognitive impairment and glucose-uptake defects induced by amyloid-β in mouse brain through inhibiting GSK-3β activity. In this study, we evaluated the effect of CT-1 on cognitive impairment induced by brain insulin resistance in mice fed a HFD, and explored its potential mechanism. CT-1 (1 μg/day, intracerebroventricular injection) was given for 14 days to mice that were fed with either a HFD or normal diet for 18 weeks. After 20 weeks of treatment, our results showed that in the HFD group, CT-1 significantly improved learning and memory deficits and alleviated neuroinflammation demonstrated by decreasing brain levels of proinflammatory cytokine tumour necrosis factor-α and interleukin-1β, and increasing brain levels of anti-inflammatory cytokine IL-10. CT-1 significantly reduced body weight gain, restored normal levels of blood glucose, fatty acids and cholesterol. Furthermore, CT-1 significantly enhanced insulin/IGF signaling pathway as indicated by increasing the expression levels of insulin receptor substrate 1 (IRS-1) and the phosphorylation of Akt/GSK-3β, and reducing the phosphorylation of IRS-1 in the hippocampus compared to control. Moreover, CT-1 increased the level of the post-synaptic protein, PSD95, and drebrin, a dendritic spine-specific protein in the hippocampus. These results indicate a previously unrecognized potential of CT-1 in alleviating high-fat diet induced cognitive impairment.
authors: Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Building 6, Anhui, Jianxi District, Luoyang, 471003, People's Republic of China, wdmzgadyx@163.com.
authors: Dongmei
authors: D
authors: Wang
authors: Ling
authors: L
authors: Liu
authors: Junqiang
authors: J
authors: Yan
authors: Wenlan
authors: W
authors: Wu
authors: Xiaoying
authors: X
authors: Zhu
authors: Yong
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000503:physiopathology / Q000517:prevention & control*; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D059305:Diet, High-Fat; D007276:Injections, Intraventricular; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D007328:Insulin; D009419:Nerve Tissue Proteins; C092073:cardiotrophin 1