Phenolic extract from BRS 305 sorghum bran increases satiety pathway through GLP-1 and MC4R gene expression in high-fat diet-induced obese mice

Sorghum is the fifth most produced cereal crop in the world. Among the different genotypes, the BRS 305 variety stands out due to its high content of phenolic compounds and condensed tannins, mainly concentrated in the bran. Phenolic compounds have shown beneficial effects on satiety through modulation of the gut-brain axis. The aim of this study was to evaluate the effect of a phenolic extract from BRS 305 sorghum bran (PE) on satiety pathway through the gut-brain axis in mice fed a high-fat diet (HF). Sorghum grains were decorticated to obtain the bran. The PE was prepared by ethanolic extraction, followed by concentration and lyophilization. The biological assay was approved by the Ethics Committee of the Federal University of Viçosa (N° 29/2024). The study was conducted in two phases. In the first, lasting 8 weeks, C57BL/6 mice were divided into two groups: AIN (n=8) and HF (n=16). In the second phase, lasting 8 weeks, animals in the AIN group continued receiving the AIN93-M standard diet, while HF animals were randomized into two groups (n=8): HF and HF+PE (HF + 0.5 g PE/kg body weight). At the end of the experiment, animals were euthanized for ileum and brain collection. Food intake was measured weekly, and feed efficiency ratio (FER%) was calculated based on total weight gain and total food consumption. Gene expression of GLP-1 and PYY in the ileum, and MC4R in the brain, was evaluated by RT-qPCR. Ileum fragments were stained for morphological evaluation. Data were analyzed by ANOVA followed by Newman–Keuls test (p0.05); however, the HF+PE group showed higher GLP-1 gene expression compared to the HF group (2.45 ± 0.30 vs. 0.33 ± 0.16) (p<0.05). In the brain, the HF+PE group exhibited higher MC4R gene expression compared to the HF group (1.41 ± 0.81 vs. 0.52 ± 0.22) (p<0.05). Regarding ileum morphology, the HF+PE group showed greater villus height compared to the HF group (133.43 ± 10.79 vs. 97.67 ± 20.67) (p<0.05). PE is rich in phenolic compounds such as 3-deoxyanthocyanidins, phenolic acids, and condensed tannins, which exhibit antioxidant and anti-inflammatory capacity, mitigating damage caused by the HF diet. Consequently, ileum morphology improved, with a possible increase in enteroendocrine cells producing incretins such as GLP-1, leading to increased anorexigenic signaling, through MC4R, and reduced food intake. Therefore, our study demonstrated that PE can reduce intestinal alterations and improve satiety through modulation of the gut-brain axis in obesity-induced animals. Acknowledgments: CAPES, FAPEMIG, CNPq, EMBRAPA.