Self-sustaining obesity

Ekaterina Korzeneva, N+1 

Joint research by British and Japanese scientists has shown that the accumulation of excess adipose tissue in the human body leads to the synthesis of a specific protein that suppresses the process of fat burning. In other words, the accumulation of fat leads to the fact that it becomes harder to "burn". The results of this study are published in the journal Nature Communications (Whittle et al., Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans).

The object of the study was mice with the LR11 gene turned off, obtained by the authors in a study on another topic. They were very different in weight from their wild counterparts. To understand the reasons for the differences in weight, both types of mice were divided into two groups: some were fed food with a high fat content, and others were fed the usual food. Further histological and pathoanatomic studies have shown that even in conditions of a "heavy" diet, mice with the LR11 gene turned off significantly underweight compared to the wild type, and in their brown fat fat droplets are much smaller. They are also protected from fatty liver infiltration.

Reduced fat content in brown adipose tissue in the presence of a high-calorie diet suggested an increase in the metabolic and heat-producing activity of this tissue in mutant mice. This was confirmed by measuring the level of a well–known marker of thermogenesis (BMP 8b) - scientists found a significant increase in its expression on a fatty diet in mice with LR11 turned off. 

Interestingly, the LR11 gene has a regulatory effect on metabolism through the soluble form of its protein (sLR11), which binds on the surface of adipocytes with two types of signaling cascade receptors that "trigger" thermogenesis and accelerate metabolism. In wild-type mice, as a result of this interaction, the entire signaling cascade is blocked and activation of metabolism becomes impossible.

The scientists also tested how applicable their observations are to human physiology, and assessed the relationship between the level of sLR11 and obesity in two cohorts of patients: in the first cohort, patients suffered from sleep disorders, and in the second – type 2 diabetes. In both groups, the total mass of adipose tissue was in direct correlation with the amount of circulating protein sLR11. In addition, a similar dependence of the degree of weight loss on a decrease in the level of sLR11 was observed in a group of patients who underwent weight loss surgery, which confirms the idea that sLR11 is synthesized by brown adipose tissue cells.

The data obtained shed light on understanding how the body protects itself from wasting energy stored in the form of excess fat. In addition, the discovered mechanism potentially makes it possible to purposefully solve the problems of both obese patients who need weight loss, and patients with anorexia, for whom its preservation is critically important.

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30.11.2015