Adipose tissue hormone reverses obesity damage – 06/26/2023 – Science

Adiponectin, a type of hormone released by adipose tissue, has a doubly important role in preserving pancreatic function: in thin people it protects beta cells, responsible for insulin secretion; and, in individuals with obesity, it reverses damage established in this tissue.

The discovery, made by researchers from the Chemistry Institute of the University of São Paulo (IQ-USP) and published in the journal Aging Cell, makes the molecule emerge as a potential therapeutic target.

Data released by the World Health Organization (WHO) in 2022 indicate that more than 1 billion people in the world are obese, with 650 million adults, 340 million adolescents and 39 million children.

In the next decade, according to the World Obesity Federation, more than half of the world’s population (about 4 billion people) will be affected by the disease, which reduces life expectancy and increases the incidence of age-related disorders. The main one is precisely the deregulation of the beta cells of the pancreas, which leads to inadequate insulin secretion and, consequently, to type 2 diabetes.

In previous tests carried out on an animal model, researchers from the Laboratory of Energy Metabolism at IQ-USP had shown that, in 24 hours, beta cells incubated with serum from thin and obese rats underwent changes: in the first case, they started to function better because their mitochondria they became more capable of producing ATP (a molecule that supplies energy to the cell) and, consequently, of signaling insulin secretion; and, in the second, its integrity was impaired, with the opposite effect.

To confirm these findings in humans, the group analyzed blood samples from lean and obese men and women from the AC Camargo Cancer Center Biobank.

“We were able to demonstrate that thin women induce a very good response with regard to cell respiration and insulin secretion and we saw that the situation was deteriorating in obese women, thin men and obese men, in that order”, reports Ana Cláudia Munhoz , first author of the article and postdoctoral fellow at IQ-USP.

“As sex and body fat seemed to be involved in the process, we raised and confirmed by laboratory experiments the hypothesis of the involvement of adipokine [hormônio liberado pelo tecido adiposo] adiponectin, which plays an important role in the regulation of mitochondria and is present in greater amounts in women.”

“For the first time, it was possible to observe that increased levels of adiponectin found in lean plasma are responsible for preserving the function of beta cells”, says Alicia Kowaltowski, professor at the Department of Biochemistry at IQ-USP and coordinator of the investigation.

“In obese people, the hormone was able to reverse 100% of the damage — one of the most remarkable scientific effects I’ve ever seen.”

The researchers point out that perhaps adiponectin is not the only missing factor in the blood of obese people, since diabetes is a multifactorial disease. It is, however, a heavyweight agent with the ability to modulate beta cell function.

therapeutic target

The study, which was supported by FAPESP through two projects (13/07937-8 and 20/06970-5), reinforces the importance of finding molecular mechanisms involved in obesity and its connection with other health problems in order to improve the treatment and break the stigma: it is a disease, with personal and genetic factors, in no way related to lack of personal control. It also represents another step towards understanding important related issues, such as, for example, its different occurrence in men and women.

Regarding beta cells specifically, the discovery brings two pieces of good news for the future. First, it indicates that problems arising from obesity are treatable; and, second, they can be modulated in the short term, opening up a promising opportunity for the development of new therapeutic strategies.

“Adiponectin itself cannot be used in treatments because it is a protein already present in large quantities in the body, unlike insulin. However, it indicates a new route for which new therapeutic molecules can be designed”, believes Kowaltowski. “We have already started to study, for example, drugs that are known to activate processes mediated by this hormone.”

The researchers, however, insist on emphasizing that, for now, there is no treatment capable of increasing adiponectin in the blood, other than losing weight and reducing central adiposity through caloric restriction and exercise.

“It is important to remember that no product eventually created for this purpose has scientific backing at the moment. Therefore, it is worth paying attention to the false promises of internet charlatans”, warns Munhoz.

The article Adiponectin reverses β-Cell damage and impaired insulin secretion induced by obesity can be read here.