Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats

• Published in: Journal of Diabetes and Metabolic Disorders
• Main Author: Chellammal H.S.J.; Hasan M.H.; Kshirsagar R.P.; Musukula V.K.R.; Ramachandran D.; Diwan P.V.
• Format: Article
• Language: English
• Published: Springer Science and Business Media Deutschland GmbH 2022
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85134498785&doi=10.1007%2fs40200-022-01074-4&partnerID=40&md5=95b0c94aafd199cb65e387de7347d7f4

Objectives: Glucose intolerance and insulin resistance are hallmarks of metabolic syndrome and lead to Alzheimer’s disease (AD). The purpose of this study is to elucidate the neuroprotective effect of metformin through insulin regulation with cardiometabolic and neurotransmitter metabolic enzyme regulation in high-fat, high-sucrose diet and streptozotocin (HFHS-STZ)–induced rats. Methods: Male Wistar rats were treated with metformin (180 mg/kg and 360 mg/kg). STZ (35 mg/kg i.p.) injection was performed on the 14th day of 42 days of HFHS diet treatment. Brain neurotransmitter metabolic enzymes (acetylcholinesterase and monoamine oxidase) were determined along with sodium-potassium ATPase (Na+K+-ATPase). Plasma lipids and homeostasis model assessment of insulin resistance (HOMA-IR) was performed. Mean arterial blood pressure, heart rate and electrocardiogram (QT, QTc and RR intervals) were analysed with PowerLab. Results: Metformin treatment significantly (p < 0.001) reduced the HOMA-IR index and decreased neurotransmitter metabolic enzymes such as AChE and MAO (p < 0.01 and p < 0.05). The lipid profile was significantly (p < 0.001) controlled with cardiometabolic functions. Conclusions: Our investigation revealed that metformin has a remarkable role in regulating brain insulin, vascular system with monoaminergic metabolic enzymes and enhancing synaptic plasticity. Metformin may be a selective early therapeutic agent in metabolic syndrome associated with cognitive decline. © 2022, The Author(s), under exclusive licence to Tehran University of Medical Sciences.