Obesity research center publishes in Endocrine Reviews

Research group is only Brazil's second to publish in world's most important endocrinology journal.

By Elton Alisson

Agência FAPESP – Researchers at the Obesity and Comorbidities Research Center (OCRC), one of the Research, Innovation and Dissemination Centers (RIDCs) supported by FAPESP, have published a thematic review article in the latest issue of Endocrine Reviews, a journal of the Endocrine Society.

The group of Brazilian researchers is the country’s second to publish an article in Endocrine Reviews, considered the world’s most important endocrinology journal, with an impact factor of more than 20.

“In Brazil, only a group of researchers at the University of São Paulo had previously published an article in this journal, about 15 years ago, according to our records,” said Lício Augusto Velloso, a professor at the University of Campinas Medical School (FCM-UNICAMP) and coordinator of OCRC.

“I believe we were invited to publish now because of the large number of studies we’ve performed in the last 20 years in an endeavor to identify the mechanisms that link diets very rich in saturated fat with the development of diabetes and obesity,” Velloso told Agência FAPESP.

In the article, the researchers at OCRC highlight the role of toll-like receptor 4 (TLR4) in triggering inflammation of various tissues in the human body and in favoring the development of obesity and diabetes.

Over the past 20 years, Velloso’s group at FCM-UNICAMP has discovered that TLR4 is activated by the saturated fat present in many foods that are part of a typical contemporary diet.

When activated, TLR4 triggers inflammation of metabolically important cells in the liver, fatty tissue, hypothalamus and muscles.

Because of this inflammation, hormones that play an important role in keeping blood sugar levels stable, such as insulin, or in controlling hunger and energy expenditure, such as leptin, cease to function properly, favoring the development of obesity and diabetes.

In recent years, another group of researchers at FCM-UNICAMP, led by Professor Mário Saad, has found that changes in the gut microbiota can weaken the integrity of the intestinal barrier. This leads to an increase in leakage of lipopolysaccharide (LPS) and fatty acids, which can activate TLR4 sufficiently to trigger systemic tissue inflammation (read more at http://agencia.fapesp.br/21306).

The authors of the article say that their data “place TLR4 in the center of the events that connect the consumption of dietary fats with metabolic inflammation and insulin resistance.”

For the past several years, the researchers at OCRC have focused on extending the characterization of these mechanisms, with the aim of contributing to the development of more efficient medications for the treatment of obesity and diabetes.

“In our view, the studies we’ve conducted in recent years, linking metabolic inflammation with the development of obesity and diabetes, can contribute to the identification of good pharmacological targets for the treatment of these diseases,” Velloso said.

The article, “TLR4 at the crossroads of nutrients, gut microbiota, and metabolic inflammation” (doi: 10.1210/er.2014-1100), by Velloso et al., can be read by subscribers to Endocrine Reviews at press.endocrine.org/doi/full/10.1210/er.2014-1100.