Life Sciences & Biotechnology
Title : | Investigating the effect of adiponectin repetor 2 (AdipoR2) agonism on non alcoholic fatty liver disease (NAFLD); a POC study for assessing the potential for AdipoR2 as a novel therapeutic target |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Medical Sciences, Metabolic Disorders |
Principal Investigator : | Dr. Sabyasachi Sanyal, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, Uttar Pradesh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | sanyal@cdri.res.in |
Details
Executive Summary : | NAFLD, a term for hepatic problems caused by hepatic fat accumulation, affects around 25% of the global population and is primarily caused by disrupted hepatic stress response to excessive nutrients like fructose, glucose, and fatty acids. Liver de novo lipogenesis converts these nutrients into fatty acids, while beta-oxidation is reduced, and excess fatty acids esterize with glycerol to form triglyceride and store as lipid droplets in hepatocytes. NAFLD and its progression to NASH involve inflammation, prolonged oxidative stress, and mitochondrial dysfunction. The standard therapy mainly consists of lifestyle modification, with pharmacotherapeutic choices being rare. The only approved drug in India is saroglitazar, which was originally marketed for type 2 diabetes and received DCGI approval for NAFLD in 2020. Adiponectin, an adipokine with insulin-sensitizing and anti-inflammatory functions, mediates its action through its receptors (AdipoR1/2), primarily expressed in the liver. Despite its immense therapeutic promise, translation has been challenging due to its large peptide size and complex multimerization properties. The only possible way to realize its translational promise is to find small molecule AdipoR agonists. This project aims to evaluate the anti-NAFLD functions of ACG in various preclinical in vitro and in vivo models, establishing AdipoR2 as a novel NAFLD therapeutic target. The hypothesis is that selective modulation of AdipoR2 activity by ACG may ameliorate NAFLD and its progression, providing a critical point of contact for AdipoR2-based NAFLD pharmacotherapy. |
Co-PI: | Prof. Naibedya Chattopadhyay, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, Uttar Pradesh-226031, Dr. Kumaravelu Jagavelu, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, Uttar Pradesh-226031 |
Total Budget (INR): | 63,45,740 |
Organizations involved