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

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Abstract

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.

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Acknowledgements

The authors acknowledge the technical support of Mr. Soji Alade and Mrs. Olaiya Oluranti of Department of Physiology, Afe Babalola University.

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C. Badejogbin is a postgraduate student under the joint supervision of O. Adeyanju and I. Adeosun; K. Olaniyi and O. Adeyanju conceived and designed the experiments. C. Badejogbin and O. Adeyanju conducted the experiments and K. Olaniyi contributed in statistical and data analyses. C. Badejogbin and D. Areola both wrote the manuscript and O. Adeyanju revised and edited the same. All authors read and approved the manuscript for publication.

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Correspondence to Oluwaseun A. Adeyanju.

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The investigation was conducted in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and was approved by the University ethical review committee, with protocol identification number NHREC17/12/2018, and every effort was made to minimize both the number of animals used and their sufferings.

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The authors declare that they have no conflicts of interest.

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Badejogbin, C., Areola, D.E., Olaniyi, K.S. et al. Sodium butyrate recovers high-fat diet-fed female Wistar rats from glucose dysmetabolism and uric acid-associated cardiac tissue damage. Naunyn-Schmiedeberg's Arch Pharmacol 392, 1411–1419 (2019). https://doi.org/10.1007/s00210-019-01679-2

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