Efeitos do extrato da Euterpe oleracea Mart. (Açaí) na indução da termogênese e na biogênese mitocondrial no tecido adiposo marrom de camundongos submetidos à dieta hiperlipídica

Abstract

The rising rates of obesity and overweight represents an urgent public health concern and are a major risk factor for metabolic syndrome. Excess lipids favor energy imbalance, leading to remodeling of adipose tissue and suggesting a directly association with the induction of obesity. Brown adipose tissue (BAT) is related to the dissipation of energy in the form of heat during adaptative thermogenesis, contributing to energy expenditure. The açaí seed extract (ASE) promotes an anti-obesity effect, whose mechanisms are still poorly understood. Therefore, the objective of this work is to evaluate the effects of treatment with ASE on BAT remodeling and its role in thermogenesis induction and mitochondrial biogenesis in BAT, as well as adipocytes proliferation and differentiation, and fatty acid utilization. Male C57BL/6 mice were divided into three groups: control (10% lipid diet); HF (60% lipid diet) and HF+ASE (60% lipid diet + 300 mg/kg/day by intragastric gavage). The diet was administered concurrently with the treatment for 12 weeks. Body mass were measured weekly and blood glucose every fifteen days during the treatment period. The lipid profile, expression of markers related to differentiation and proliferation, thermogenesis, mitochondrial biogenesis and fatty acids utilization, as well as the activity of antioxidant enzymes and oxidative damage in BAT homogenate were evaluated. The morphological alterations of BAT and white adipose tissue (WAT) were analyzed histologically. ASE proved to be effective in preventing body mass gain, blood glucose and morphological changes in white and brown adipose tissue in mice treated with the extract when compared to the HF group. In BAT, ASE treatment prevented the increased expression differentiation markers PRDM16 and PPARα, thermogenesis induction pAMPK, pLKB1, SIRT-1, UCP-1 and β3-AR, fatty acid utilization PLIN1, ATGL, HSL and CPT-1, and mitochondrial biogenesis PGC-1α and NRF1 in relation to the HF group. The increase in UCP-1 protein expression in the group treated with ASE was corroborated by immunostaining of this protein. In addition, ASE treatment also showed a reduction in oxidative damage through a reduction in MDA levels compared to the HF group and a reduction in 8-isoprostane immunostaining, as well as increased activity of the antioxidant enzyme SOD, without changing the enzymatic activity of GPx and catalase in the treated group in relation to the HF group. The extract also prevented the increase of inflammatory markers MCP-1 and TNF-α in BAT. These findings demonstrate that treatment with ASE prevented structural changes in the BAT of high-fat fed mice and increased the expression of key proteins related to thermogenesis and mitochondrial biogenesis, in addition to reducing oxidative stress in BAT, suggesting that extract can be used as an important approach in preventing obesity