Phenolic extract from BRS 305 sorghum bran improves brain leptin signal in high-fat diet-induced obese mice

Abstract: Obesity is strongly associated with leptin resistance, a condition characterized by impaired leptin signaling that disrupts energy homeostasis, contributing to excessive weight gain and adiposity. Sorghum (Sorghum bicolor) is a cereal rich in phenolic compounds, including 3-deoxyanthocyanidins and phenolic acids, which have demonstrated anti-obesity and metabolic regulatory effects. However, the effects of sorghum phenolic compounds on leptin signaling pathways remain poorly understood. This study mainly to investigate whether phenolic extract from BRS 305 sorghum bran (PE) modulates leptin signaling in mice fed a high-fat diet. PE was obtained from BRS 305 sorghum bran using 80% ethanol extraction followed by concentration and freeze drying. Male C57BL/6 mice were initially fed either AIN-93G (n=8) or high-fat diet (HF) (n=16) for 8 weeks to induce obesity. Subsequently, animals were redistributed into three groups for an additional 8-week treatment period: AIN, HF, and HF+PE (0.5g PE/kg body weight). Final body weight was measured at the end of the treatment phase. Total adiposity was calculated from inguinal, epididymal, abdominal, and brown adipose tissue depots. Brain leptin receptor (LEP-R) gene expression was determined by RT-qPCR, and leptin concentration was quantified by ELISA. Statistical analyses were performed using one-way ANOVA followed by Newman–Keuls post-hoc test and unpaired Student’s t-test for HF versus HF+PE comparisons (p<0.05). All procedures were approved by the Ethics Committee of the Federal University of Viçosa (Protocol 29/2024). The HF+PE group presented lower final body weight (35.87 ± 0.92 vs. 41.91 ± 1.53 g) compared to the HF group, while the AIN group presented the lowest body weight (p<0.05). The HF+PE and AIN groups presented lower body adiposity compared to the HF group (9.10 ± 0.54 and 9.47 ± 0.84 vs. 10.65 ± 0.89%) (p<0.05). In addition, the HF+PE group presented an increased brain LEP-R gene expression compared to HF and AIN groups (p<0.05), while for the brain leptin concentration the HF+PE group presented a lower concentration compared to the HF and AIN groups (p<0.05). The HE+PE body weight and adiposity may be associated with the action of phenolic compounds present in the sorghum extract, particularly 3-deoxyanthocyanidins and phenolic acids, which have been reported to present antioxidant and anti-inflammatory properties that can modulate pathways involved in appetite control, inflammation, and energy metabolism. This modulation can increase brain LEP-R expression together with the reduction in brain leptin concentration suggests an improvement in leptin sensitivity. These findings reinforce the potential role of sorghum phenolic compounds in regulating obesity-related metabolic dysfunctions through modulation of leptin signaling pathways. Phenolic extract from BRS 305 sorghum bran reduced body weight and adiposity while improving markers associated with leptin signaling in obese mice, indicating its potential as a dietary strategy to attenuate obesity-related leptin resistance. Acknowledgments: CAPES, FAPEMIG, CNPq, EMBRAPA.