Anti-Obesity Therapeutic Targets Studied In Silico and In Vivo: A Systematic Review.

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.

Nanoparticles Containing Tamarind Isolate Protein Potentiate the Satiety without Promoting the Anti-Inflammatory Effect in a Preclinical Model of Diet-Induced Obesity.

The study aimed to evaluate the nanoparticles (ECW) containing tamarind trypsin inhibitor (TTI) concerning the storage effect under different conditions on antitrypsin activity and the bioactive potential in a preclinical model. ECW was exposed to different pH and temperatures to evaluate the interaction between TTI and its encapsulating agents, monitored by antitrypsin activity. Wistar rats (n = 25) with obesity induced by diet were divided into groups: untreated; treatment with nutritionally adequate diet; treatment with nutritionally adequate diet and ECW/12.5 mg/kg; treatment with ECW/12.5 mg/kg; and treatment with TTI/25 mg/kg. The groups were evaluated over ten days with regards to satiety, zoometric, biochemical, and inflammatory parameters, using ten times less TTI (2.5 mg/kg) contained in ECW. TTI was protected and encapsulated in ECW without showing residual inhibitory activity. Only at gastric pH did ECW show antitrypsin activity. At different temperatures, it showed high antitrypsin activity, similar to TTI. The animals treated with ECW had significantly reduced body weight variation (p < 0.05), and only TTI treatment reduced the inflammatory parameters significantly (p < 0.05). The study showed that by using lower concentrations of TTI in ECW it was possible to perceive promising effects with perspectives of use in functional products for managing obesity and its complications.