The discovery of a brain protein that helps decide whether the body should store or burn fat could lead to medications that help maintain weight loss, according to research led by Monash University in Australia.
To the chagrin of hard-working dieters worldwide, losing excess weight has the contradictory effect of inducing long-term changes to the body's biochemistry that make maintaining a newfound healthy size extremely difficult. Appetite-managing hormones that are acclimated to years of overeating are known to cue feelings of hunger even in instances where enough daily fuel has been consumed, while energy-managing hormones will order the body to immediately convert any extra food into new fat deposits.
Though this may sound like cruel metabolic self-sabotage, the body is really just trying to protect itself from a perceived threat of starvation. And even a willpower of steel is little defense against the hardwired survival process.
“Obesity is not a lifestyle disease. That’s the absolute opposite of what it is," said study author Zane Andrews to the Sydney Morning Herald. “Throughout evolution we have naturally selected people who are better at becoming fat. Our genes have evolved to make us fatter.”
The exact interplay between the brain, the pancreas (where insulin and its counterpart glucagon are produced), and the digestive tract has yet to be described. However, it is known that specialized cells called AgRP neurons monitor levels of glucose and other fuel sources throughout the tissues and subsequently make decisions about what the body should do next.
The Australian study, published in Cell Reports, deepens our understanding with the finding that an enzyme called carnitine acetyltransferase (Crat) helps AgRP neurons in mice manage the transition from a period of dieting to normal food consumption levels.
Mice who were genetically engineered to lack the gene for Crat showed higher-than-normal rates of converting stored forms of fuel molecules into ready-for-consumption glucose during a phase of food restriction. The mice also displayed increased fatty acid metabolism in the liver.
After the mice were allowed to feed freely again, mice without Crat continued to burn fat, whereas normal mice quickly began to only metabolize the incoming glucose from their food.
“Our current studies suggest that Crat affects AgRP neuronal function predominantly during fasting and the transition to refeeding,” the authors write. “Beyond calorie intake, it is becoming clear that the inappropriate handling of nutrient 'fate' is largely responsible for metabolic disease, and this study shows that Crat in AgRP neurons has an unappreciated role in this process.”
Of course, future investigations will need to prove that the same pathway occurs in humans, something that is not as definite as some headline-grabbing research would lead you to believe. But if a similar process does occur in human AgRP cells, the team is optimistic about potential applications.
"Manipulating this protein offers the opportunity to trick the brain and not replace the lost weight through increased appetite and storage of fat," Andrews said in a statement.