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The "hunger trick" of our ancestors, which has become a "curse" – 18/07/2019

Molecular "cunning" that has hindered our ancient ancestors from starvation may contribute to the current outbreak of obesity, according to new research by the New York University Medical School.

During the famine, the researchers explain in the article published in Cell Reportsanimals are more likely to survive if they can accumulate and stretch the accumulated energyEven if an animal has secured a banquet, evolution has favored it by storing the excess fuel as fat before it can be quickly seen again in the absence of food.

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– We found a mechanism against hunger, which has become a curse in a time of abundance because it thinks that the cellular stress created by overeating is similar to hunger-induced stress and slows down our ability to burn fat, warns the lead author of the study, Dr. Anne Marie Schmidt, PhD in Endocrinology at the Medical Faculty. from the University of New York.

The work reveals that the natural function of a protein called RAGE on the surface of fat cells is to stop the decomposition of stored fats against stress. In March 2017, the American Heart Association (AHA) announced a donation to help researchers Find an explanation for the "Metabolic Brake",

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The AHA Funds follow a 2016 study in which it was found that the AHA participants "The Biggest Loser in America" (one reality show American like Argentina "Weight Question") They recovered their lost kilos once the program is over. Why does your metabolism stop when you lose weight, as if their bodies were inclined to return to obesity?

According to the authors, the most effective way for evolution to create an anti-hunger mechanism is from ancient systems that help animals use food to get cellular energy and recover from injury. The adrenaline hormone, which signals the conversion of fat into energy when animals flee from predators or generate heat in the body when they are cooled, is also associated with these primary mechanisms.

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This approximation, by the same signaling proteins, means this RAGE can block the "burning" of fat what is required when we die of hunger, we freeze, we hurt, we panic or, ironically, we overeat.

According to the new study and experiments conducted elsewhere in human tissues, RAGE is activated with advanced AGEs that occur when blood sugar is combined with proteins or fats, most of the elderly, people with diabetes, and / or with obesity. Other molecules also activate RAGE, such as those that are released when cells die and disperse their contents into intracellular spaces in response to stress.

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An alarming opportunity, Schmidt says, is that many proteins and fats have activated the destruction of RAGE, as they deform and accumulate (as toxic oligomers) in people who eat more than their ancestors.

The present study found that Removing RAGE from fat cells has led mice to gain up to 75% less weight during the three months of high-fat meals, regardless of equal amounts of food and physical activity than mice with RAGE in activity.

Transplantation of fat that does not have RAGE in normal mice also reduces weight gain when eating high fat.

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In both sets of experiments, removing RAGE from the fat cells releases braking mechanisms that limit energy consumptionOnce released, the energy expenditure increases, which contributes to reducing the body weight gain in oily diet mice.

The new study complements the discovery of the team of experimental compounds that adhere to RAGE's "tail". From there, they prevent you from rejecting the action of protein kinase A, a key player in the chain reaction that ends with a protein called UCP1 that converts fat into body heat.

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The research team plans, after optimizing the design of these "RAGE inhibitors", to investigate whether agents can prevent patients with barrier surgery and those who undergo medical weight loss schemes to recover their loss.

Researchers note that RAGE is much more active during metabolic stress (for example, dying of hunger or overeating) than in a daily function, suggesting that This can be safely obstructed by medicationaccording to the authors.

"As RAGE evolves outside of the immune system, blocking can also reduce the inflammatory signals that contribute to insulin resistance that drives diabetes," says Schmidt, "and such treatments can reduce the inflammation of the entire system, with the risk of atherosclerosis, cancer and Alzheimer's disease ".

(Source: DPA)

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