Protein can ‘cheat’ weight gain caused by fats – 08/25/2023 – Equilibrium

A US study has revealed new facts about the body’s processes of fat metabolism, indicating a new treatment strategy for metabolic diseases such as obesity and diabetes. The researchers identified, from tests on mice, that a complex of proteins called AMPK is deactivated when the individual receives a “supernutrition”, but that it is possible to “bypass” this system by eliminating its inhibitor from the organism.

A high-fat diet induces the body to produce SAPS3, a substance that is part of protein phosphatase 6 and which “turns off” AMPK. The authors found, however, that by removing SAPS3 from the body or liver, mice with high consumption of fatty foods were protected from the harmful effects of these meals, as the metabolic changes were reversed.

In mice with balanced diets, in turn, the removal of SAPS3 did not cause any change. The results were published in the journal Nature Communications by researchers from the University of California Irvine (UCI) and the oncological hospital City of Hope National Medical Center, in the USA.

The research points out that, when excluding the inhibitor from the individual with a fatty diet, the AMPK is reactivated and resumes its metabolism regulatory function, better controlling a process called “homeostasis”.

“Our results reveal that SAPS3 is a negative regulator of AMPK and its suppression works as a gatekeeper when the metabolism is disturbed. It represents a potential therapeutic strategy to treat metabolic syndromes”, they state in the article.

Metabolic nutritional balance

AMPK senses the body’s nutrition and works to keep it balanced. According to a note released by the UCI, when this complex of proteins, for example, “detects that blood glucose is low, it can increase the breakdown of lipids to produce energy in their place”.

Eating large amounts of fat blocks this complex activity and causes the imbalance that leads to conditions such as diabetes or obesity.

To find out how this regulation worked, UCI biologists deleted SAPS3 from the genome of a group of mice and fed them meals with 45% fat.

In the UCI statement, Mei Kong, professor of molecular biology and biochemistry and corresponding author of the study, said the results surprised the team. “Removing the SAPS3 inhibitor component released AMPK activation in these mice, allowing them to maintain a normal energy balance despite eating a lot of fat,” he said.

In practice, this meant that mice that ate a lot of fat still maintained normal weight, avoiding obesity and the development of diabetes. Ying Yang, project scientist, in turn, pointed out to the UCI that the proposal for a new therapy is based on blocking the inhibition and reactivation of AMPK in people.

“It can help overcome disorders such as obesity, diabetes, fatty liver disease and others,” he says. The next step is to develop molecules that can inhibit SAPS3 to restore the balance of metabolism that has not had its genome altered. They should also study the role of SAPS3 in other conditions of disturbed metabolic systems, such as cancer and aging.

The projection of the WHO (World Health Organization) is that, by 2025, about 2.3 billion adults around the world will be overweight, which is equivalent to say one in three people or 32.5% of the population from the planet. Of these, 700 million will be obese, with a body mass index (BMI) above 30.

Nationally, according to the Obesity Map of the Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso), it is estimated that half of the population (55.4%) is already overweight (BMI equal to or greater than 25). Obesity affects almost a fifth of Brazilians (19.8%).

Endocrinologist Renato Zilli, a member of the Brazilian Society of Endocrinology and Metabology (SBEM) and the Clinical Staff of Hospital Sirio Libanês, recalls that overweight and obesity are multifactorial and that the body tends to maintain the maximum weight achieved.

“Weight control in the brain is a strict thing. The person weighs 70 kilos and, when it reaches 74 kilos, the brain understands that that is the setpoint and will always try to return to that ever higher value”, points out Zilli.

According to the expert, to maintain this milestone, the body changes our perception of food and also how we metabolize what we eat – and that is why it is so difficult to lose weight when you are overweight. “The brain starts to save calories, it makes food tastier, it seems to make you want more when you eat less. People often understand this as a lack of character, but it is a complex thing, it involves several factors, behavioral, genetic, lack of sleep and the environment,” says endocrinologist

In the case of fat, the expert says that consumption generates inflammation in the body, affecting the intestinal microbiota, blood vessels and the brain itself. For Zilli, the discovery of new therapies against obesity is positive, but improving nutrition, physical activity and sleep quality will still be necessary and a priority to keep overweight and obesity rates lower.

“This study [norte-americano] showed that by altering the genome of mice and knocking out the expression of this protein, there was no impact of fat [no corpo]. It’s more of a metabolic pathway, but lifestyle change is still the most important. Medication does not work alone, medication is an adjuvant”, he reinforces.