Revision required
Restoring sensitivity to the "satiety hormone" helped in the fight against obesity
Maria Azarova, Naked Science
A team of scientists from the Universities of Michigan, Colorado and Vanderbilt (United States of America) found that inhibitors of a cytosolic enzyme called histone deacetylase 6, acting as powerful sensitivity enhancers to the hormone leptin, help fight obesity in mice. The results of the study are published in the journal Nature Metabolism (Çakır et al., Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity).
Obesity is a scourge of the XXI century and one of the most acute public health problems, especially in developed countries. According to experts, two out of three American adults are overweight, one in three is obese. These figures are even higher among ethnic minorities, rural populations and people with low incomes. The health risks associated with excess body fat include a higher incidence of cardiovascular disease, diabetes, multiple cancers, hypertension, high cholesterol, asthma, osteoarthritis, and liver disease.
As scientists explain, during the accumulation of excess energy in the form of fat in animals, including mice and humans, fat cells secrete more leptin into the bloodstream, which then enters the brain. This "satiety hormone" allows you to control the energy balance of the body by sending signals to the hypothalamus, and eventually regulate appetite while increasing energy consumption. The main task of leptin is to help maintain weight. Its content in the body is directly related to the amount of fat: if a person gains extra pounds, hormone levels will increase, and vice versa.
The paradox is that obese people, despite hyperleptinemia, become resistant to the action of leptin: it ceases to affect appetite and energy expenditure. At the same time, when its levels drop with weight loss, we may start to feel hungrier, and the weight loss process will slow down.
The discovery of the authors of the new study, who conducted experiments on mice, is that they found a way to make their subjects more sensitive to leptin and eventually start losing weight. Rodents with obesity caused by the consumption of high-fat foods were given a selective inhibitor of histone deacetylase 6 encoded by the HDAC6 gene.
In a few weeks, the body weight of the study participants from the first group, unlike the control group, decreased by almost 25 percent due to the restoration of sensitivity to leptin. Plus, the weight loss occurred almost entirely due to adipose tissue and with the preservation of muscles. Skinny mice who were given the same compound did not lose weight, as did fat mice whose bodies were not genetically capable of producing leptin. From this, scientists concluded that high levels of the "satiety hormone" are initially necessary to suppress HDAC6 and combat obesity.
"Our results suggest the presence of adipokine regulated by HDAC6, which serves as an agent that increases sensitivity to leptin. HDAC6 is a potential target for the treatment of obesity," the scientists explained. In addition to losing weight, the mice showed an improvement in overall metabolic health: for example, they had increased glucose tolerance, which indicates a lower risk of developing diabetes.
However, according to the researchers, their results cannot yet be used to treat obesity in humans. The problem is that most potent HDAC6 inhibitors can be toxic when a part of the molecule is destroyed in the human body. To eliminate this obstacle, the authors of the work create HDAC inhibitors that do not have a potentially toxic component, but retain the same activity against HDAC6 in rodents.
Portal "Eternal youth" http://vechnayamolodost.ru