Obesity is reversible
Genetic regulators of obesity found in hibernating animals
Polina Loseva, N+1
The researchers compared the genomes of 4 animals from different orders that hibernate, and found they have common parts of the genome that evolve faster than average. Most of them are needed to regulate the work of genes and are located next to the genes that are responsible for the development of obesity in humans. The work was published in the journal Cell Reports.
Obesity is not only the deposition of adipose tissue, but also a whole complex of symptoms associated with metabolism. At the same time, the resistance of cells to insulin is increased, which can lead to the development of type 2 diabetes. At the same time, the activity of the immune system increases and chronic inflammation occurs. All this together becomes a risk factor for the development of a whole range of diseases – from heart attack to cancer and dementia.
The causes of obesity are still not completely clear. There are about 250 sections of the human genome and 123 genes that are somehow related to it, in particular, the FTO locus (fat mass and obesity, fat mass and obesity). However, it is unknown which of them is responsible for metabolism.
Elliott Ferris and Christopher Gregg from The University of Utah has proposed an elegant approach to the study of this problem. They turned their attention to mammals that are capable of hibernation. At the same time, their body weight increases by 30-50 percent and their insulin resistance increases – that is, in some way they reproduce the symptoms of obesity. But at the same time, they do not have hypertension and inflammation. It turns out that obesity does not turn out to be a pathology, and besides, it is reversible – by summer, animals lose weight back.
It is logical to assume that animals that hibernate have some kind of internal metabolic switch. At the same time, this is hardly due to the appearance of a new gene, since hibernation developed independently in representatives of 7 orders of mammals. Most likely, they have the same genes, but have somehow learned to regulate their work and control their obesity.
Ferris and Gregg worked with four species of mammals: the lesser tenrec (a relative of hedgehogs), the brown moth (bat), the thirteen-striped ground squirrel and the mouse lemur. Scientists decided to look for regulators of obesity in these animals among the rapidly evolving regions of the genome (AR, accelerated regions) – these are areas that are conservative in themselves, that is, they are preserved in different groups, but their sequence mutates especially often.
The researchers identified 537,189 conservative sites in the mammalian genome and found that among them there are rapidly evolving ones: 17,228 in the moth, 5119 in the ground squirrel, 7661 in the lemur and 17917 in the tenrek. Then they picked up seven animals from the same groups that do not hibernate, and they also identified rapidly evolving areas. After that, the scientists checked in which cases the number of matching areas in two animals is higher than if this coincidence was random. In all pairs of animals that hibernate, it turned out to be non-random (p=0.0387), unlike sleeping-sleepless or sleepless-sleepless pairs, even after adjusting for evolutionary kinship. Tellingly, most of these areas turned out to be outside the genes, that is, most likely, they are responsible for regulating their work.
After that, the scientists checked next to which genes the rapidly evolving regions are located. They found that these regions were more common (p=0.0002) next to genes that are associated with obesity in humans (including the FTO locus) than with any other genes, including those similar in size and sequence.
As a model of the abnormal work of the "obesity genes" in humans, the authors of the work took the Prader-Willi syndrome. This is a genetic disease, which, among other things, is characterized by overeating and obesity since childhood. The researchers used data from previous studies, the authors of which compiled a list of abnormally active genes in the cells of patients with Prader-Willi syndrome. For these genes, scientists found analogues in animals that hibernate, and found that rapidly evolving regulatory regions are more common next to these analogues (p=0.013).
Thus, scientists have confirmed that the change in metabolism, which ultimately leads to obesity, can be caused by the activity of regulatory sites, and their set is similar in all mammals that hibernate. Then you can try to selectively block the work of these areas in animals and look for the main switch of obesity among them.
Hibernation is a tremulous and difficult process: for example, black bears sleep worse if they eat human food. There are literally several species of primates that are capable of hibernation, although their hibernation is similar in all respects to that of other mammals – for example, they need to get out of it to go to sleep. And more recently, doctors managed to immerse a person in artificial hibernation for the first time – in order to gain time for an emergency operation.
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