Adiponectin may be a potential therapeutic target for obesity and diabetes

Adiponectin, a hormone secreted by adipose tissue, plays a doubly important role in maintaining the function of the pancreas: in lean people, it protects beta cells, which make insulin, and in obese people obesity, it reverses adipose tissue damage. The discovery was made by researchers at the Institute of Chemistry of the University of São Paulo (IQ-USP) in Brazil and is reported in a paper published in the journal Nature. cell agingsuggests that adiponectin is a potential therapeutic target.

More than 1 billion people are obese worldwide, according to data provided by the World Health Organization (WHO) by 2022: 650 million adults, 340 million adolescents and 39 million children. About 4 billion people, or more than half of the world’s population, will be affected by the disease over the next decade, the World Obesity Federation predicts. Obesity reduces life expectancy and increases the incidence of age-related dysfunctions, especially deregulation of pancreatic beta cells leading to inadequate insulin secretion and type diabetes. 2.

In previous animal model tests, researchers at IQ-USP’s Energy Metabolism Laboratory have shown that beta cells incubated with serum from lean and obese mice have undergo changes in a 24-hour period. In lean mice, the performance of beta cells was improved because their mitochondria were better able to produce ATP and signal insulin secretion. ATP is an important energy-carrying molecule that fuels cellular functions. In obese mice, the integrity of beta cells was impaired, with the opposite effect.

To confirm these findings in humans, the team analyzed blood samples from lean and obese men and women provided by the AC Camargo Cancer Center, an important institution in the City of São Paulo. . “We were able to demonstrate that thin women respond well as far as cellular respiration and insulin secretion is concerned, and the situation worsens in obese women as well as in men,” said Ana Cláudia Munhoz. skinny and obese, in that order.” first author of the paper and a postdoctoral fellow at IQ-USP. «Gender and body fat appear to be involved in this process, suggesting involvement of adiponectin, which is important for mitochondrial regulation and is more abundant in women. Trials in Our lab confirmed this hypothesis.»

«We found that increased amounts of adiponectin in lean plasma are responsible for maintaining beta-cell functions. This is the first time an observation has been made. In the plasma of obese people, this hormone repaired 100% damage, one of the most severe cases.» Alicia Kowaltowski, final author of the paper and professor in IQ-USP’s Department of Biochemistry.

According to the researchers, adiponectin may not be the only missing blood component in obese individuals, since diabetes is a multifactorial disease, but it has important implications for its ability to regulate function. function of beta cells.

treatment goals

The results of the study, supported by FAPESP through two projects (13/07937-8 and 20/06970-5), reinforce the importance of learning more about the molecular mechanisms involved in obesity. obesity and their links to other health problems. This will help improve treatment and combat the «low self-control» stigma, proving once again that obesity is a disease caused by individual and genetic factors.

They also represent another step in understanding key aspects of obesity, such as different prevalence rates in men and women.

For beta cells in particular, this finding bodes well for the future, as it shows that the problems arising from obesity are treatable and can be mitigated in a relatively short time, opens up promising opportunities for the development of new therapeutic strategies.

“The appropriate adiponectin cannot be used therapeutically because this protein is already abundant in the body, unlike insulin, but it does point to a pathway by which new therapeutic molecules could be engineered,” Kowaltowski said. next». «We’ve started studying drugs that are known to trigger these hormone-mediated processes, for example.»

However, the researchers stress that there are currently no treatments capable of increasing blood levels of adiponectin, other than weight loss and central fat loss by restricting calorie intake and exercise. sex. «It’s important to remember that there are currently no products sold as obesity drugs that have any scientific basis,» warns Munhoz. «Patients should be careful to avoid being promised by internet quacks,» warns Munhoz. appointment».


São Paulo Research Foundation (FAPESP)

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