Unicamp researchers show that a diet rich in saturated fat damages the brain's hunger control system
While investigating the factors associated with the growing global obesity epidemic over the past decade, scientists have identified two events that strongly contribute to weight gain.
One of them is the change in the profile of bacteria that make up the intestinal flora. Studies published between 2005 and 2007 showed that obese people generally have a set of microorganisms that favor the absorption of nutrients from the diet. In other words, an apple can be more caloric for a fat person than for a thin person. But whether this is a cause or a consequence of being overweight is still unknown.
Another important event is the death of a group of neurons in a region of the brain called the hypothalamus. Known as POMC neurons, these cells are nutrient sensors and have the function of warning the body that it is time to stop eating and that there is energy available to spend. After the loss of these sensors, studies have shown, individuals increasingly feel the need to consume foods rich in fat and sugar. On the other hand, their metabolism slows down and stores a large part of the energy provided by an unbalanced diet.
“We then began to ask ourselves: what comes first? Is the change in the patient's eating pattern caused by an error in the brain's hunger control system or a change in the intestinal microbiome? Our most recent data suggests that the hypothalamus is damaged long before changes occur in the intestine”, said Licio Augusto Velloso, coordinator of the Center for Research in Obesity and Comorbidities (OCRC) from Unicamp, one of the CEPIDs supported by FAPESP.
In a lecture presented today (19), during the FAPESP Week Nebraska-Texas, Velloso presented results from a study carried out at the Faculty of Medical Sciences (FCM) at Unicamp during the post doctoral by Daniela Razolli.
The group carried out a series of temporal analyzes on the tissues of mice subjected to a diet rich in saturated fat – which in total lasted four months, long enough for the animal to become obese. At various times throughout the experimental period, part of the colony was sacrificed and its brain and intestine were analyzed by researchers.
“We began to detect hypothalamic changes on the first day of the obesogenic diet. The changes in the intestinal microbiota took between two and three weeks to appear. It’s a relatively large temporal difference – considering they are mice”, explained Velloso.
In previous studies, the Unicamp group had already detailed how damage to POMC neurons occurs. The saturated fat molecules ingested are absorbed in the intestine, fall into the bloodstream and reach the brain, along with the other nutrients in the diet.
In the central nervous system, a defense cell known as microglia understands that excess fat is a threat to neurons and begins to produce inflammatory molecules as if it were fighting a pathogen.
“This inflammation initially impairs the correct functioning of hypothalamic neurons. If it lasts for a long time, the cells end up dying. This is probably the reason why individuals who remain obese for a long time have difficulty losing weight and relapse into the disease even after several treatments. These people simply can no longer achieve a balance of energy flow in the body”, commented Velloso.
As the experiment with mice showed, neuronal damage begins long before the individual begins to gain weight, but can be reversed early in the process. If the dietary error persists, said Velloso, the neuronal damage becomes irreversible.
“If the individual eats a meal rich in saturated fat, but then spends several days on a diet rich in fiber and vegetables, inflammation in the hypothalamus decreases and neurons recover. What cannot happen is that the obesogenic diet becomes frequent, as this leads to a gradual increase in the inflammatory process”, said the researcher.
An unbalanced diet modifies a series of metabolic parameters, favoring the development of diabetes and hypertension. In this context, Velloso explained, there is a change in the intestinal microbiota which, in turn, contributes to both the worsening of obesity and the diseases associated with it.
According to Velloso, studies by other groups have shown that a diet rich in simple carbohydrates, such as those present in sugar and white flour, can also raise blood lipid levels and, indirectly, promote inflammation in the hypothalamus.
“When comparing the two types of diet, however, researchers concluded that the results are worse when there is excessive consumption of saturated fat,” said Velloso.
The main source of saturated fat in the human diet is foods of animal origin, such as fatty meats, butter and dairy products. But this nutrient is also present in coconut oil and derivatives and palm oil, as well as in several industrialized products, including cookies, ice cream, cakes and pies.
Neurogenesis
According to Velloso, recent work suggests that it is possible to promote neurogenesis in the hypothalamus, that is, to stimulate the emergence of new POMC neurons in an attempt to combat obesity. But for now, this is just an experimental possibility, tested on laboratory rodents. Much research is still needed to understand how the cell differentiation process can be controlled.
“We are at the stage of understanding how neuron precursor cells, a type of stem cell that exists in the brain, work. We need to find out which factors need to be activated to trigger the process of neurogenesis. It’s an initial step, but it could be a therapeutic solution for obesity in the future,” said Velloso.
Producing food to promote health
Held between September 18th and 22nd, FAPESP Week Nebraska-Texas aims to foster collaboration between scientists from Brazil and the United States.
This morning, right before Velloso's talk, North American researcher Andrew Benson presented the scope of the The Nebraska Food for Health Center, created about a year ago with the aim of developing new foods capable of promoting health by acting mainly on the intestinal microbiome.
“Our food production system is currently concerned with reducing costs, increasing productivity, using resources efficiently and other factors. But concerns about health appear only when it comes to safety. In other words, the system is concerned with not killing people and not promoting health. We need to change this paradigm,” said Benson.
The idea, according to the researcher, is to study the genetic diversity of local crops, mainly soybeans, beans and other grains, to identify components present in these foods that are capable of beneficially influencing the profile of bacteria in the intestine. In the future, the most promising compounds could be isolated and added to other types of processed foods.
This approach could, in Benson's assessment, help combat metabolic, autoimmune, cardiovascular diseases, cancer, inflammatory bowel diseases and even neurological and lung diseases.
“We have a plan for the next 10 years. For the first five, we will be focusing on our local cultures and diseases. In the second half we will address the problem globally and for this we will need international partners”, he highlighted.
Read more
http://www.unicamp.br/unicamp/unicamp_hoje/ju/agosto2009/ju437pdf/Pag09.pdf
http://www.unicamp.br/unicamp/unicamp_hoje/ju/marco2009/ju421pdf/Pag05.pdf