Sodium butyrate arrests pancreato-hepatic synchronous uric acid and lipid dysmetabolism in high fat diet fed Wistar rats.

High fat diet (HFD) is a risk factor for metabolic syndrome which is characterized by overt glucose dysmetabolism and tissue derangement. The liver and pancreas are important metabolic tissues with anatomical proximity sharing splanchnic and mesenteric circulation but it is unclear whether, there is an associated metabolic status between the two organs in health and disease. Uric acid (UA) hypersecretion and ectopic lipid accumulation are characteristic pathophysiology of an array of non-communicable diseases. Sodium butyrate (BUT) is reputed for therapeutic roles in metabolic derangement. Therefore, the present study investigated synchrony in hepatic and pancreatic UA and lipid metabolic status in HFD-induced glucose dysregulation and probed the beneficial effects of BUT. Twenty-four female Wistar rats were treated with normal rat chow and distilled water (po) or sodium butyrate (200 mg/kg; po) or high fat diet and distilled water (po) or high fat diet and sodium butyrate. Results showed that HFD increased plasma, pancreatic and hepatic triglyceride, triglyceride-glucose index, malondialdehyde, uric acid (UA), lactate dehydrogenase but reduced glucose-6-phosphate dehydrogenase. Histological analysis revealed hepatic and pancreatic architectural derangement and cellular degeneration in HFD-fed animals. However, BUT reversed the HFD-induced systemic, pancreatic and hepatic synchronous dysmetabolism with evidence of improved histology. HFD-induced lipid and UA alterations were synchronous in the pancreas and liver. BUT elicits beneficial effects on systemic and tissue HFD-induced deleterious metabolic changes which were synchronized in pancreas and liver of rats.

Sodium butyrate recovers high-fat diet-fed female Wistar rats from glucose dysmetabolism and uric acid-associated cardiac tissue damage.

Increased global consumption of high-fat/high-calorie diet has led to higher incidence of the multifactorial cardiometabolic syndrome especially among women. The links between glucose deregulation and eventual mortal cardiac diseases are still being investigated. However, several reports have implicated elevated uric acid (UA) in the progression of metabolic disorders especially during high-fructose diet. Also, butyrate (BUT) a short-chain fatty acid is being identified with intriguing therapeutic potentials in metabolic disorders. We therefore hypothesized that high-fat diet-induced glucose deregulation and cardiac tissue damage are associated with elevated UA and attenuated by BUT in female rats. Twenty-four 10-week-old female Wistar rats with weights ranging from 135 to 150 g were treated with normal rat chow and distilled water (po) or sodium butyrate (200 mg/kg; po) or high-fat diet and distilled water (po) or high-fat diet and sodium butyrate. Treatments lasted for 6 weeks. Results showed that high-fat diet caused glucose dysmetabolism, elevated plasma triglyceride (TG), total cholesterol (TC), corticosterone, malondialdehyde (MDA), plasma and cardiac UA, and lactate dehydrogenase (LDH). High-fat diet also led to depressed reduced glutathione (GSH). Histological analysis of cardiac tissue showed cellular infarction, infiltration, and fibrosis in high-fat diet-fed rats. However, all these effects were ameliorated by BUT treatment. The findings here showed that high-fat diet resulted in glucose dysmetabolism and cardiac tissue damage through a UA-dependent mechanism and that BUT can protect against high-fat diet-induced cardiometabolic disorders through UA suppression and augmentation of glutathione antioxidant defenses.