WHOLE SORGHUM BRS 305 FLOUR MODULATE SATIETY AND IMPROVES ANTIOXIDANT RESPONSE IN BRAIN AND ADIPOSE TISSUE IN WISTAR RATS FED WITH HIGH-FAT HIGH FRUCTOSE DIET

Sorghum BRS 305 (Sorghum bicolor L. Moench) consumption can reestablish the physiological activity of pathways related to satiety and antioxidant response in the brain due to its high content of tannins and resistant starch. The objective of the study was to investigate the bioactive properties of whole sorghum BRS305 flour on satiety markers and antioxidant response in adipose tissue and brain of rats fed with a high-fat and fructose diet. This study was divided into two phases. Male Wistar rats were allocated into two groups for 8 weeks, control (n=8), or high-fat and fructose diet (HFHF) (n=16), to induce metabolic changes. In second phase, animals of control group received the same diet, and animals of HFHF group were divided into two groups: HFHF (n=8) and HFHF + sorghum flour (n=8), for 10 weeks. The gene expression of markers of satiety and antioxidant response in adipose tissue and brain were analyzed by RT-PCR. Antioxidant activity was measured by SOD (superoxide dismutase) and catalase activity. Interactions between anthocyanins identified in sorghum flour with markers of inflammation and satiety were evaluated by molecular docking, using AutoDock Vina. Data were submitted to ANOVA followed by Newman-Keuls (α=0.05). This study was approved by the Animal Use Ethics Committee of UFV (CEUA/UFV), protocol No.38/2019. The experimental groups that received HFHF diet presented lower total food consumption in the treatment phase compared with the control group. Consumption of sorghum flour did not alter adiponectin gene expression. As for markers related to satiety centers, sorghum reduced the gene expression of leptin, resistin, and CB1 (endocannabinoid receptor 1) in adipose and brain tissues compared to HFHF group. In brain, sorghum consumption also promotes a reduction in NPY (neuropeptide Y) gene expression. In general, consumption of sorghum flour improves antioxidant response, reducing PPARγ (peroxisome proliferator-activated receptor gamma) and SIRT1 (Sirtuin 1) gene expression in adipose tissue and enhancing the PPARα gene expression and SOD and catalase activity in brain, compared to HFHF. Furthermore, sorghum flour consumption resulted in an increase in HSP72 (Heat Shock Protein72) and NRF2 (Nuclear factor erythroid 2-related factor 2) gene expression, which are markers of antioxidant response. In silico analysis of interaction between anthocyanins from sorghum and satiety markers showed interaction with PPARα, CB1, and leptin receptors. Consumption of a high-fat and high fructose diet is associated with changes in satiety hormones, such as leptin and resistin, which lead to a detrimental effect on hypothalamic leptin signaling, resulting in hyperleptinemia and hyperactivation of brain receptors for leptin receptor and type 1 endocannabinoid receptor. Anthocyanins present in sorghum BRS 305, have been identified as antioxidant mechanisms capable of reducing oxidative stress, as observed in this study. Content of resistant starch and condensed tannins, associated with anthocyanins profile, can directly lead to the resensitization of hypothalamic leptin receptors, aiding in the reversal of hyperleptinemia. Sorghum consumption can improve leptin disturbances caused by high-fat and fructose diet consumption and enhance antioxidant response in brain of rats fed with this diet, which can benefit hormonal control of hunger and satiety.