Micro RNA 23a-3p and 146a-5p Confers Selective Modulation of PPARγ Activity by Alleviating Cellular Adiposity Without Increasing Plasma Glucose Level in Mouse Model

Abstract

Background: Obesity is a complex multi-factorial metabolic disorder, mostly manifested with higher levels of circulating fatty acid derivatives and glucose. Medications that counteract obesity pose severe adverse effects and vary in efficacy. In this work, we systematically investigated how micro RNAs could regulate the process of adipogenesis by focussing on glucose and lipid metabolic pathways.

Methods: Potential role of miRNAs in regulating lipogenesis in vitro were evaluated. In vivo effects of selected miRNAs were tested in HFD fed C57BL/6J mice models using synthetic mimics.

Findings: Preliminary screening by bioinformatics tools and cell culture based experiments proved that micro RNA 23a-3p and 146a-5p effectively reduced adipocyte lipid content without inhibiting the glucose uptake of cells. Mechanistic studies have shown that these miRNAs can affect the expression of Steroid Responsive Co-Activators (SRCs) and Liver X - Receptor - α (LXRα), thereby regulating the activity profile of PPARγ during adipogenesis. Intra-peritoneal injection of miR-mimics reduced total body weight, visceral fat content and serum free fatty acid level, without increasing the blood glucose level. 

Interpretation: Four consecutive injections of Mmu-miR-23a-3p and 146a-5p in respective mice groups were found to be effective in reducing obesity and its complications. This can be a lead in designing prospective therapeutic strategy in obesity treatment by site specific regulation of adipogenesis.

Funding Statement: This work is supported by the intramural funding from Rajiv Gandhi Centre for Biotechnology, Department of Biotechnology, Govt. of India. MK has received funding from Science and Engineering Research Board (SERB), Department of Science and Technology, Govt. of India.

Declaration of Interests: The authors declare no conflict of interest.

Ethics Approval Statement: All animal studies were approved by the Institute Animal Ethics Committee of Rajiv Gandhi Centre for Biotechnology (No.IAEC/2014/82). We have followed the guidelines given by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA).