Xanthohumol restores hepatic glucolipid metabolism balance in type 1 diabetic Wistar rats

Diabetes is a major public health problem worldwide. Beer-derived xanthohumol exhibits anti-inflammatory, anti-angiogenic and antiapoptotic effects, three processes exacerbated in diabetes. Thus, we propose to identify molecular mechanisms associated with hepatic glucolipid metabolism imbalance in type 1 diabetic Wistar rats and to evaluate the effect of xanthohumol-enriched stout beer consumption in these pathways. Eight week-old healthy male Wistar rats were divided into five groups (n=6 each): diabetic rats drinking water; treated with 5% ethanol; treated with stout beer; treated with stout beer supplemented with 10mg xanthohumol/L; and healthy rats drinking water (control group). Type 1 diabetes was induced by an intraperitoneal injection of streptozotocin. After 48h the diabetic condition was confirmed by measuring blood glucose content (>250mg/dL). The animals were euthanized 5 weeks later. Hepatic H&E, PAS, Reticulin and Sirius Red histological staining were performed and quantified using ImageJ®. Expression of pACC/ACC ratio and FAS levels were evaluated by Western blotting. Diabetic rats showed liver glycogen reduction, and increased apoptosis and fibrosis compared to control group. Xanthohumol consumption attenuated these three parameters to control values. Lipogenesis was assessed by pACC/ACC and FAS expression. Increased pACC/ACC ratios and decreased FAS levels were found in diabetic rats. Xanthohumol reverted the expression of these two metabolic enzymes. Xanthohumol consumption interfered with liver catabolic state seen in type 1 diabetes, reverting glycogen depletion, enhancing lipogenesis and attenuating apoptosis and fibrosis, implying an effect in inf lammation. Altogether these findings reveal that xanthohumol can be a therapeutic agent against liver metabolic changes in type 1 diabetes, playing a possible role in the insulin receptor pathways.