Uric Acid-Associated Cardiac Tissue Damage Caused by High Fat Diet Is Reversed by Sodium Butyrate

Abstract

Objective: 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. Design and method: 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: 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. Conclusions: The findings here showed that high-fat diet resulted in glucose dysmetabolism and cardiac tissue damage through a uric acid (UA) - dependent mechanism and that butyrate (BUT) can protect against high-fat diet-induced cardiometabolic disorders through UA suppression and augmentation of glutathione antioxidant defenses. This study therefore demonstrates that UA is involved in high fat diet-induced cardiometabolic syndrome. However, data here shows that the UA - associated events in high fat diet will chronically engender cardiac tissue damage. Interestingly, with UA suppression, BUT treatment showed plausible beneficial glucoregulatory, anti-inflammatory and antioxidant properties which were potent enough to confer protection on the cardiac tissue preventing overt damage in high fat diet-fed rats. Therefore, BUT may be considered for the development of suitable therapeutic candidate in the treatment of metabolic syndrome and cardiac derangements associated with heightened UA.