According to a recent study conducted by researchers from the University of Eastern Finland, alternative splicing of genes associated with obesity and type 2 diabetes might contribute to obesity’s pathophysiology.
Obesity is a condition that leads to alteration in the splicing pattern of the genes TCF7L2 and INSR, causing impaired insulin action. Nevertheless, these changes can be reversed by a very low-calorie diet or by obesity surgery. The discovery, presented by Dorota Kaminska, MSc, as part of her doctoral dissertation, increases the understanding of splicing dysfunctions in obesity, which can lead more accurate diagnosis and targeted treatments for metabolic disorders.
Type 2 diabetes and obesity are complicated conditions caused by environmental, lifestyle and genetic factors.
Obesity is associated with other metabolic problems such as diabetes and resistance to insulin, but the underlying mechanisms linking obesity and type 2 diabetes remain poorly understood.
The mechanism by which a gene produces more than one protein is called alternative splicing, and this process occurs in the majority of humans’ genes, compensating the reduced amount of genes in the human genome. In this new research, the focus was on the exploration of the effects of weight loss and obesity on the alternative splicing process of the genes INSR and TCF7L2.
The researchers also discovered alternatively spliced genes in the regions of genes related with the risk of obesity, and found that specifically the genes TCF7L2, INSR and MSH5 in the subcutaneous fat is regulated by weight loss. The authors also discovered that body mass index is a key factor of the splicing of the genes TRA2B, BAG6 and MSH5 in subcutaneous fat.
The study was conducted at the Department of Clinical Nutrition of the University of Eastern Finland, and data was sought from the European Network on Functional Genomics of Type 2 Diabetes (EUGENE2) studies, from the Kuopio Obesity Surgery (KOBS), and a study exploring very low calorie diet (VLCD), Metabolic Syndrome in Men (METSIM).
According to the researchers modulation of alternative splicing can potentially lead to the development of new treatments targeting phenotype associated with obesity.