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Physiology

Fat attracts fat

The fatty acid found in red meat causes the death of neurons that control the appetite

Remedios1HÉLIO DE ALMEIDAAnyone who likes a rare steak and particularly the layer of white fat that surrounds it should perhaps be worried. A type of fat – the saturated long chains of fatty acids, found mainly in red meat – may be one of the causes of obesity. According to experiments carried out on mice, these molecules cause inflammation in the hypothalamus, located at the base of the brain, which leads to the destruction of the neurons that control appetite and the burning of calories. “Perhaps we’ve found an explanation for the difficulty obese people have of controlling their hunger and losing weight, even when they try strict diets to get thinner”, says Lício Velloso, a researcher from the State University of Campinas (Unicamp), who coordinated this study that was published in January in the Journal of Neuroscience.

Previous studies by Velloso’s team and by other groups had shown that obesity was a disease that began in the brain or the muscles and was caused by diets that are heavy in sugars or fats. This excess generates a resistance to insulin, which carries glucose to the cells where it is transformed into energy, and leads to continuous food consumption (Pesquisa FAPESP nº 140). Tests on animals had already shown that diets rich in fats generally caused more serious damage to the hypothalamus than those rich in sugars. To see which type of fat was most harmful the researchers from Unicamp injected different types of animal or vegetable fatty acid into the hypothalamus of mice. The fats from soy oil were shown to have a mild effect on the brain, while animal fats and to a lesser extent the fat found in peanut oil had the most harmful effect.

The saturated fatty acid molecules bond with surface proteins, called TLR-2 and TLR-4, of a type of cell called microglias, which protect the neurons of the hypothalamus against viruses and bacteria, according to the experiment carried out by Marciane Milanski, under the guidance of Velloso. Once activated the TLR-2 and, less intensely, the TLR-4 stimulate the production of other proteins known as cytokines. Normally, in other parts of the body, cytokines stimulate the production of antibodies and specialist cells for fighting viruses, bacteria and tumors. In the hypothalamus the cytokines produced in this way destroy the neurons that control appetite and the burning of calories. “What was not known was what could be setting off this inflammation that leads to neuron death”, says Velloso. This month Juliana Contin Moraes, whose tutor is Velloso, should present her PhD thesis showing, by means of six different analysis techniques, neuron death caused by inflammation that is activated by these specific types of fat.

TLR-4 was a target of old. In previous experiments mice with a genetic mutation that switches off this protein became less fat, and did not develop insulin-resistance even when submitted to a diet that was excessively rich in lipids (fats). TLR-4 activation also explains a phenomenon that was observed years ago in Velloso and Mario Saad’s laboratories at Unicamp: the greater than normal production of enzymes that prevent insulin from working. This protein now represents the connection between diets that are rich in fats and the development of insulin-resistance, which may facilitate the development of obesity, diabetes, hypertension and cardiovascular diseases. Even cancer may develop more easily in people who are unhealthily overweight.

A person is considered to be overweight when the body mass index (BMI, obtained by dividing the weight by the square root of the height) is from 25 to 29.9 kg/m2 and obese when the BMI is equal to or greater than 30 kg/m2: so, for example, a person who is 1.70 meters tall is obese if he weighs more than 87 kilos. According to a survey by the IBGE based on the population in Brazil in 2003, 41.1% of all men and 40% of the women are overweight and 8.9% of the men and 13.1% of the women are obese.

Anyone who likes to eat meat with fat should be asking themselves what they must do to avoid this situation. Velloso believes that undoubtedly reducing their consumption of fats can help, but again there is no information about how much fat begins to kill neurons, or if this domino effect of reactions can be contained or reversed. “Obese people, whose organisms continually re-establish the point of equilibrium, run the risk of never again going back to their previous equilibrium, where their weight is stable”, says Velloso. The still far-off answer would be to find anti-inflammatory medication that is capable of acting only on the hypothalamus and as a response to the stimuli generated only by long-chain saturated fatty acids, in order to avoid defense cells failing to react when a virus or bacteria appears.

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