One of the "obesity genes" is being studied at NSU

Novosibirsk physiologists are investigating possible ways to treat genetic forms of obesity

Dmitry Pasechnik, Anastasia Anikina, NSU

Anna Kuleshova, a student of the Faculty of Natural Sciences (FEN) of Novosibirsk State University, and Yulia Piskunova, a graduate of the FEN, are studying the effect of the "satiety hormone" leptin on the expression of genes that control metabolism in obese mice at the Institute of Cytology and Genetics (ICiG) SB RAS. In the future, the results of the study can be used in the treatment of overweight problems in people.

According to the World Health Organization, in 2014, more than 1.9 billion adults over the age of 18 were overweight, of which over 600 million were obese. The number of obese people in recent years exceeds the number of underweight people – this situation is observed in all regions of the world, except for some areas of sub-Saharan Africa and Asia.

The Laboratory of Physiological Genetics of the Institute of Cytology and Genetics SB RAS studies the influence of genetic factors and hormones on metabolic processes in the body in the prenatal (before birth) and postnatal (after birth) periods. Anna Kuleshova, a student of the Department of Physiology of the FEN NSU, and Yulia Piskunova, a graduate of the FEN, are investigating the effect of the peptide hormone leptin, which is also called the "satiety hormone", on the expression of genes that control metabolism in obese mice.

Leptin is a peptide hormone produced by adipose tissue, which is involved in the regulation of the body's energy metabolism and body weight. Activates the receptors of the hypothalamus, thereby normalizing metabolism. Presumably, a decrease in leptin concentration leads to obesity.

In mice , the presence of the yellow mutation often indicates
yellow coat color

 – A section of the gene called agouti, which may contain the yellow mutation found in humans and small rodents. This mutation leads to the fact that the body begins to produce agouti protein that blocks the receptors of the hypothalamus. At the same time, there is an increase in appetite and a decrease in energy consumption. And with age, such mice and people have problems with excess weight, – says Anna Kuleshova.

Previously, it was believed that since the mutation blocks the receptors of the hypothalamus, leptin cannot perform its function through them. But, according to Anna Kuleshova, in 1997, a group of scientists conducted studies that showed that even with the presence of the agouti yellow mutation, leptin can work. Before the development of obesity in mice due to this mutation, leptin contributes to weight loss and activation of kidney nerves.

– We are conducting a study of the effect of leptin on carbohydrate-fat metabolism in mice with the yellow mutation even before the development of obesity. The novelty of the work lies in the fact that we analyze the expression level of key genes of carbohydrate-fat metabolism, which has not been studied before, – explain Anna Kuleshova and Yulia Piskunova.

In the summer of 2016, employees of the Laboratory of Physiological Genetics of ICIG SB RAS organized the necessary experiments.

Synthesized leptin was injected under the skin of mice with the yellow mutation at the age of nine weeks before the development of obesity. In the blood of experimental rodents, the level of insulin, glucose (as indicators of carbohydrate metabolism) and triglycerides and fatty acids (indicators of the intensity of fat metabolism) were measured. If there was a difference between the analyses of experimental and control groups of mice, a genetic study was conducted: the expression level of key genes of carbohydrate-fat metabolism was determined by analyzing RNA isolated from brown and white adipose tissues of mice, as well as skeletal muscle tissue.

At the moment, a statistical calculation is being carried out, which will allow comparing changes in the gene expression of experimental animals with the control group and with rodents having the same mutagen, but not participating in the experiment.

– Our research is more fundamental than applied. As previous studies show, manipulation with leptin can have a therapeutic effect on people with obesity, but now it is very expensive in terms of accessibility. New data on the expression of genes with the yellow mutation in the future will be able to help in the search for a way to treat obesity in people with such a mutation, – emphasizes Anna Kuleshova.

Portal "Eternal youth" http://vechnayamolodost.ru  15.12.2016