Banca de QUALIFICAÇÃO: ANA JÚLIA FELIPE CAMELO AGUIAR

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANA JÚLIA FELIPE CAMELO AGUIAR
DATE: 23/02/2026
TIME: 09:00
LOCAL: Videoconferência
TITLE:

Proteins and peptides as therapeutic tools for obesity: effect of tamarindisolated trypsin inhibitor (TTI) on the enterohepatic axis.

KEY WORDS:

Tamarindus indica L.; computational simulation; systematic review; C57BL/6 mice; MASLD; trypsin inhibitors.

PAGES: 102
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Obesity is a multifactorial chronic disease strongly associated with metabolic dysfunction–associated steatotic liver disease (MASLD). This study aimed to investigate the therapeutic potential of natural bioactive proteins and peptides in obesity management. The thesis was structured in two complementary chapters. The first comprised a systematic review designed to answer the research question: “Which peptides or proteins have been used to treat obesity in in silico studies?”, structured according to the PECo framework and assessing the agreement between in silico findings and subsequent in vitro and/or in vivo validation. The search followed PRISMA-P guidelines and was registered in PROSPERO (CRD42022355540). Out of the 1,015 identified records, seven met the eligibility criteria. The analyzed peptides were derived from diverse natural sources, and all studies employed molecular docking approaches. Among the included studies, 46.15% were classified as having an unclear risk of bias. Pancreatic lipase was the primary molecular target (n = 5), with all peptides demonstrating inhibitory activity corroborated by in vitro and/or in vivo assays. Additionally, some peptides were identified as PPARγ and PPARα agonists (n = 2). The findings highlight the effectiveness of computational simulations as screening tools to guide experimental investigations and accelerate the discovery of novel anti-obesity peptides. The second chapter described a preclinical study evaluating the effects of tamarind seed trypsin inhibitor (TTI) on the enterohepatic axis in high-fat diet–induced obese C57BL/6 mice. TTI was isolated by affinity chromatography (Trypsin-Sepharose) and characterized by 12% SDSPAGE and specific inhibitory activity (IU/mg). Male C57BL/6 mice (n = 60), healthy or obese, were allocated into six groups (n = 10/group): healthy control (CS), healthy + TTI (CI), obese control (HFS), obese + standard diet (HFD), obese + TTI (HFI), and obese + standard diet + TTI (HFDI). TTI-treated groups received 25 mg/kg/day by oral gavage for 14 days. Data were expressed as mean ± SD, tested for normality (Shapiro–Wilk), and analyzed using ANOVA/Tukey or Kruskal–Wallis/Dunn tests, as appropriate (p ≤ 0.05). TTI exhibited 100% inhibitory activity, with a specific antitryptic activity of 11,178.8 IU/mg. In vivo, TTI reduced food (p < 0.05) and energy intake (p < 0.05), with the HFDI group showing the greatest weight loss (9%). Improved glucose tolerance at 120 minutes was observed in CI (p < 0.05) and HFDI (p < 0.05), alongside reduced insulin resistance (HOMA-IR) in HFI (p < 0.001) and CI (p < 0.001), and lower fasting glycemia in CI (p < 0.001). Lipid metabolism and cardiovascular risk markers improved, evidenced by a lower total cholesterol/HDL-c ratio in HFDI (p = 0.05). Furthermore, obese groups treated with TTI showed marked reductions in hepatic steatosis (HFI, −58%, p < 0.001; HFDI, −66%, p < 0.001) and increased goblet cell numbers (HFI, +34%, p < 0.001; HFDI, +45%, p < 0.0001). These findings demonstrate that TTI exerts beneficial metabolic effects by modulating the enterohepatic axis and represents a promising bioactive compound for the treatment of obesity and MASLD.

COMMITTEE MEMBERS:
Presidente - 1149356 - ELIZEU ANTUNES DOS SANTOS
Externa ao Programa - 2374605 - AURIGENA ANTUNES DE ARAUJO - UFRNExterno ao Programa - 2859541 - PEDRO PAULO DE ANDRADE SANTOS - UFRN