Blood-derived miRNA levels are not correlated with metabolic or anthropometric parameters in obese pre-diabetic subjects but with systemic inflammation

• Type of Material: Article
• Authors: Prabu Paramasivam, World Health Organization; Emmanuelle Meugnier, Claude Bernard University; Kuppan Gokulakrishnan, National Institute of Mental Health and Neurosciences; Harish Ranjini, World Health Organization; Lisa Staimez, Emory University; Mary Weber, Emory University; Kabayam Venkat Narayan, Emory University; Hubert Vidal, Claude Bernard University; Nikhil Tandon, Centre for Chronic Disease Control and Public Health Foundation of India; Dorairaj Prabhakaran, Emory University; Anjana Ranjit Mohan, World Health Organization; Viswanathan Mohan, World Health Organization; Sophie Rome, Claude Bernard University; Muthuswamy Balasubramanyam, World Health Organization
• Language: English
• Date: 2022-02-04
• Publisher: Public Library of Science (PLoS)
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Paramasivam et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0263479
• Title of Journal or Parent Work: PLoS One
• Volume: 17
• Issue: 2
• Grant/Funding Information: This work was supported by the FRENCH – INDIAN COUNCIL OF MEDICAL RESEARCH (ICMR) COOPERATION (INSERM – ICMR PROGRAM, 2014-2017) as well as grant support from the Department of Biotechnology (DBT), Government of INDIA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Research Categories: Health Sciences, Public Health; Biology, Genetics; Health Sciences, Nutrition

Abstract

As blood-derived miRNAs (c-miRNAs) are modulated by exercise and nutrition, we postulated that they might be used to monitor the effects of a lifestyle intervention (LI) to prevent diabetes development. To challenge this hypothesis, obese Asian Indian pre-diabetic patients were submitted to diet modifications and physical activity for 4 months (LI group) and compared to a control group which was given recommendations only. We have considered 2 periods of time to analyze the data, i.e.; a first one to study the response to the intervention (4 months), and a second one post-intervention (8 months). At basal, 4 months and 8 months post-intervention the levels of 17 c-miRNAs were quantified, selected either for their relevance to the pathology or because they are known to be modulated by physical activity or diet. Their variations were correlated with variations of 25 metabolic and anthropometric parameters and cytokines. As expected, fasting-glycaemia, insulin-sensitivity, levels of exercise- and obesity-induced cytokines were ameliorated after 4 months. In addition, the levels of 4 miRNAs (i.e.; miR-128-3p, miR-374a-5p, miR-221-3p, and miR-133a-3p) were changed only in the LI group and were correlated with metabolic improvement (insulin sensitivity, cytokine levels, waist circumference and systolic blood pressure). However, 8 months post-intervention almost all ameliorated metabolic parameters declined indicating that the volunteers did not continue the protocol on their own. Surprisingly, the LI positive effects on c-miRNA levels were still detected, and were even more pronounced 8 months post-intervention. In parallel, MCP-1, involved in tissue infiltration by immune cells, and Il-6, adiponectin and irisin, which have anti-inflammatory effects, continued to be significantly and positively modified, 8 months post-intervention. These data demonstrated for the first time, that c-miRNA correlations with metabolic parameters and insulin sensitivity are in fact only indirect and likely associated with the level systemic inflammation. More generally speaking, this important result explains the high variability between the previous studies designed to identify specific c-miRNAs associated with the severity of insulin-resistance. The results of all these studies should take into account the level of inflammation of the patients. In addition, this finding could also explain why, whatever the pathology considered (i.e.; cancers, diabetes, neurodegenerative disorders, inflammatory diseases) the same subset of miRNAs is always found altered in the blood of patients vs healthy subjects, as these pathologies are all associated with the development of inflammation.