Ações terapêuticas do caroço do açaí na obesidade: estudo comparativo com a metformina sobre o eixo intestino-hipotálamo

Abstract

Obesity increases morbidity and mortality by affecting several systems in the human body, increasing the risk of metabolic disorders such as impaired glycemic homeostasis, intestinal barrier dysfunction, and alterations in the gut microbiota. Furthermore, obesity often disrupts gut-hypothalamus axis communication. The hydroalcoholic extract of açaí seeds (ASE), rich in phenolic compounds, has demonstrated beneficial effects on obesity and hyperglycemia; however, its effects on gut health and gut-hypothalamus communication remain unclear. Metformin, which is widely prescribed for hyperglycemia, is known to influence intestinal health and obesity-related outcomes. In this study, we evaluated the effects of ASE compared to metformin in C57BL/6 mice with diet-induced obesity (DIO). Mice were assigned to four groups: C (10% fat diet), HF (60% fat diet), HFA (60% fat diet + ASE, 300 mg/kg), and HFM (60% fat diet + metformin, 300 mg/kg). After 10 weeks on the diets, treatments were administered for 4 weeks while diets were maintained. Both ASE and metformin significantly reduced body weight compared to HF mice. DIO-induced hyperglycemia was improved by both treatments, with ASE exhibiting a stronger effect on fasting glucose levels. In the Jejunum, DIO caused increased inflammation and oxidative damage, a reduced villus-to-crypt ratio, and decreased intestinal alkaline phosphatase expression. ASE particularly improved inflammation markers. In the ileum, DIO reduced Tight Junction protein expression and AMPK activation, which were partially restored by both treatments, with metformin showing greater efficacy. In the colon, DIO-induced mucus reduction was partially reversed by both treatments. While fasting plasma GLP-1 levels remained unchanged by DIO, leptin and LPS levels were elevated and reduced by both treatments, with metformin more effectively lowering leptin. DIO established an obesogenic microbiota profile in HF mice, which was mitigated in the treated groups. ASE increased short-chain fatty acids, including acetate and propionate, in feces. In the hypothalamus, DIO altered the expression of TLR4, GLP-1R, and anorexigenic peptides (POMC and CART). Both treatments partially mitigated these effects, reducing TLR4 and POMC expression. Metformin significantly increased ghrelin receptor expression, while ASE elevated AgRP and NPY expression. Both treatments enhanced leptin receptor mRNA levels. These findings suggest ASE and metformin are promising strategies to counteract the adverse effects of obesity on intestinal health and gut-hypothalamus communication, though they act through distinct mechanisms. Further research is needed to elucidate underlying mechanisms and identify additional markers associated with these effects.