Restoring sensitivity to the “satiety hormone” helped in the fight against obesity

(ORDO NEWS) — Obese mice given a compound that restores leptin sensitivity lost 25 percent of their original body weight.

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, which act as potent enhancers of leptin sensitivity, help fight obesity in mice. The results of the study are published in the journal Nature Metabolism .

Obesity is the scourge of the 21st century and one of the most pressing public health problems, especially in developed countries. Experts estimate that two out of three American adults are overweight, and one in three is obese.

These rates are even higher among ethnic minorities, rural populations and low-income people. Health risks associated with excess body fat include a higher incidence of cardiovascular disease, diabetes, several types of cancer, hypertension, high cholesterol, asthma, osteoarthritis, and liver disease.

As the scientists explain, in the process of storing excess energy in the form of fat in animals, including mice and humans, fat cells release more leptin into the bloodstream, which then enters the brain. This “satiation hormone” allows you to control the energy balance of the body by sending signals to the hypothalamus, and as a result, regulate appetite while increasing energy expenditure.

The main function 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, as levels drop with weight loss, we may begin 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 have found a way to make their test subjects more sensitive to leptin and eventually begin to lose weight. High-fat obese rodents were given a selective inhibitor of histone deacetylase 6 encoded by the HDAC6 gene.

Within a few weeks, the body weight of study participants from the first group, in contrast to the control group, decreased by almost 25 percent due to the restoration of leptin sensitivity. The upside is that the weight loss was almost entirely due to adipose tissue and with the preservation of muscle.

Skinny mice given the same compound did not lose weight, nor did fat mice that were not genetically capable of producing leptin. From this, the scientists concluded that in order to suppress HDAC6 and fight obesity, high levels of the “satiety hormone” are initially required.

“ Our results suggest the presence of an HDAC6-regulated adipokine that serves as a leptin sensitizing agent. HDAC6 is a potential target for the treatment of obesity ,” the scientists explained. In addition to losing weight, the mice showed improvements in overall metabolic health, such as increased glucose tolerance, which indicates a lower risk of developing diabetes.

However, according to the researchers, their results cannot yet be applied to the treatment of obesity in humans. The problem is that most potent HDAC6 inhibitors can be toxic when broken down by part of the molecule in the human body. To overcome 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.


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