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: Dongmei Wang, Ling Liu, Junqiang Yan, Wenlan Wu, Xiaoying Zhu, Yong Wang
• Journal: Neurochemical research (Neurochem Res) Vol. 40 Issue 4 Pg. 843-53 (Apr 2015) ISSN: 1573-6903 [Electronic] United States
• PMID: 25672823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Insulin
• Nerve Tissue Proteins
• cardiotrophin 1

Topics

• Animals
• Behavior, Animal
• Cognition Disorders (physiopathology, prevention & control)
• Cytokines (administration & dosage, pharmacology)
• Diet, High-Fat
• Injections, Intraventricular
• Insulin (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Nerve Tissue Proteins (metabolism)
• Obesity (metabolism)
• Signal Transduction