A growing global epidemic of obesity and its related health complications such as type 2 diabetes is the reason why scientists are focusing on finding genes that increase the risk of developing obesity in the last decade. A breakthrough was finally made with discovery of the gene for ‘leanness’.
Scientists led by Prof. Dr. Simon Horvat from the University of Ljubljana and the National Institute of Chemistry, Slovenia and Prof. Dr. Nicholas Morton from the University of Edinburgh, United Kingdom identified an important gene linked to obesity called thiosulphate sulfurtransferase (Tst). In the experiments Tst at higher expression in adipose tissue of animal models caused resistance to the development of obesity and diabetes when animals were fed with high-caloric foods. TST protein, produced by the Tst gene, is a mitochondrial matrix enzyme naturally present in human body, which in combination with thiosulfate detoxifies harmful waste products that accumulate in fat cells and protects the body from cyanide.
In the study, published in the journal Nature Medicine, researchers used a polygenic lean mouse model, which has been selected for low adiposity for 60 generations, to identify mitochondrial Tst as a candidate gene for resistance to obesity with selectively increased expression in adipocytes. They compared lean mice to overweight mice fed with the same high-caloric diet and found out that transgenic overexpression of Tst in adipocytes protected lean mice from diet-induced obesity and insulin-resistant diabetes while mice with lower expression of this gene showed noticeably worsened diabetes. Mice survived even without Tst gene but the quantity of adipose cells was increased and the level of sugar in blood was higher. Moreover, when diabetic mice were offered water with added thiosulfate to activate TST enzyme, they drank less water even though increased thirst is typical for diabetes patients. This means that negative effects of diabetes can be reduced in an animal model by stimulating the Tst gene.
The effectiveness of TST has also been demonstrated in humans. Adipocyte tissue was collected from people with different body mass indexes and it was shown that the level of TST is increased in adipose tissue of skinny and healthy people while it is reduced in obese and diabetic patients. Similarly, human cells reacted to thiosulfate as it was shown in a mouse model.
The scientists believe that by searching for more effective pharmacological agents and use of modern synthetic biology it will be possible to develop a therapy for obesity-related type 2 diabetes in the future.
By Katarina Kovac, PhD, BioSistemika LLC
Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness
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