Deciphering the Role of Cytokine IL-13 rs20541 in Ageing- and Obesity-associated Adipose Tissue Dysfunction

Obesity and aging share common chronic low-grade inflammation of the adipose (fat) tissue, involving the shift from the anti-inflammatory M2 phenotype of adipose tissue macrophages (ATMs) to the pro-inflammatory M1 phenotype. Particularly, IL-13, a cytokine which secretion is stimulated by M2 ATMs, shows beneficial roles in obesity prevention and mitigates the detrimental metabolic effects of obesity. The IL-13 gene has a structural variant, namely rs20541, which occurs at a high frequency among East Asians and its association with allergic diseases is well-established. Our preliminary study showed that rs20541 potentially contributes to obesity; however, its reproducibility and detailed biological mechanisms involved are still unknown. Objectives: To investigate the effects of rs20541 on adipose cell function and the molecular mechanisms involved, and to determine the association of rs20541 with obesity and its related phenotypes among a multi-ethnic Malaysian sample population. Research methodology: The effects of rs20541 on adipogenesis, lipolysis and glucose uptake rates will be investigated by subjecting adipose cells to recombinant protein. Whole transcriptome profile of adipose cells will also be determined by total RNA sequencing and molecular pathways affected by rs20541 will be determined by gene ontology analysis. Participants from the young (controls) and elderly will be genotyped for rs20541, and their genotypes will be associated with anthropometric, cardiometabolic and dietary profiles indicative of obesity and aging. Expected implication and output significance: This study will help to elucidate the molecular mechanisms of IL-13-mediated adipocyte tissue dysfunction in obesity and aging. New therapeutic avenues involving IL-13 cytokine manipulation in order to harness its anti-obesity and anti-aging properties will be envisioned.