Efeitos metabólicos e inflamatórios do glúten de trigo: papel da proteína na obesidade

Abstract

Objectives: Despite the popularity of gluten-free diets, an association between gluten and obesity is still controversial, and there are few controlled studies published. Previously, we showed that a gluten-free diet reduces weight gain without changing food intake in mice fed high-fat diets. In the present study, we investigated the effects of gluten intake on fat metabolism, thermogenesis and energy expenditure in mice fed a standard or a high-fat diet. Methods: C57BL/6 mice were fed a standard (Eutrophic Eut) or high-fat diet (Obese Ob) to induce obesity. EutG and ObG groups had diets containing 4.5% of wheat gluten. After eight weeks, the animals received 99mTechnetium-radiolabeled gluten (99mTc-GLU) orally to study gluten absorption and biodistribution or they underwent indirect calorimetry to study oxygen consumption (VO2) and energy expenditure. After euthanasia, brown (BAT) and subcutaneous adipose tissue (SAT) were collected to assess thermogenic and browning-related protein expression. Lipid metabolism and the inflammatory profile were studied in adipocyte cultures from the four groups. Results: Despite having had the same energy intake, EutG and ObG mice exhibited increased body weight and fat deposits (SAT and VAT visceral adipose tissue) compared with their respective controls.99mTc-GLU or its peptides were detected in the blood, liver and VAT, suggesting that it can reach extra-intestinal organs. Uncoupling protein 1 (UCP1) expression was reduced in the BAT of Ob-G and in the SAT of EutG and ObG mice. In SAT of EutG and ObG groups there was also a reduction in BMP7 expression (related to browning which is the differentiation of brown adipocytes in white adipose tissue). Indirect calorimetry showed lower VO2 in EutG and ObG groups compared with their controls. In obese mice, daily energy expenditure was reduced with gluten intake. Gluten also reduced adiponectin, peroxisome proliferator-activated receptor (PPAR) and PPAR and hormone-sensitive lipase in cultures of adipocytes isolated from Ob mice, while in the EutG group, gluten intake increased Il-6 expression and tended to increase that of TNF. Conclusion: Gluten or its peptides can reach extra-intestinal organs, such as liver and VAT, supporting a direct effect on those sites. The inclusion of wheat gluten in isocaloric diets decreases thermogenesis, browning and energy expenditure, and accelerates weight gain and adiposity in eutrophic and, mainly, in obese mice. Keywords: wheat gluten; obesity; thermogenesis; calorimetry; adipocyte culture