Abstract

The study aimed to determine effects of a ketogenic diet on metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation, and spermatogenesis in a high-fat and high-cholesterol diet-induced obese mice model. Forty-two male C57BL/6 mice were fed either a normal diet (NC group) or a high-fat and high-cholesterol (HFC) diet (HFC group) for 16 weeks, and mice from the HFC group were later randomly divided into two groups: the first were maintained on the original HFC diet, and the second were fed a medium-chain triacylglycerol (MCT)-based ketogenic diet for 8 weeks (KD group). A poor semen quality was observed in the HFC group, but this was eliminated by the ketogenic diet. Both the HFC and KD groups exhibited enhanced apoptosis protein expressions in testis tissue, including caspase 3 and cleaved PARP, and higher inflammation protein expressions, including TNF-α and NF-κB. However, the KD group exhibited a statistically-significant reduction in lipid peroxidation and an increased glutathione peroxidase level as compared with the HFC group. The HFC diet induced obesity in mice, which developed body weight gain, abnormal relative organ weights, metabolic dysfunction, and liver injury. Overall, the results showed that a ketogenic diet attenuated oxidative stress and improved the semen quality reduced by the HFC diet.

Highlights

  • Dietary composition nowadays has shifted from being staple-based toward containing higher levels of animal-source foods and vegetable oils

  • There was no significant difference in the mean kidney weight among the three groups, but the kidney to body weight ratio in the HFC group was markedly decreased

  • In contrast to the NC group, the total cholesterol (TC) level was significantly increased in the HFC and ketogenic diet (KD) groups (NC = 52.50 ± 17.78 mg/dL, HFC = 159.44 ± 24.56 mg/dL, KD = 75.78 ± 8.18 mg/dL; p < 0.05), but the serum TC in the KD group was significantly lower than that in the HFC group

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Summary

Introduction

Dietary composition nowadays has shifted from being staple-based toward containing higher levels of animal-source foods and vegetable oils. Previous studies have shown that a higher BMI is associated with a lower live birth rate [2] and a poor semen quality [3]. The amounts and types of fat intake [4], and even serum lipids, are associated with semen quality parameters [5], and evidence from human study has demonstrated high incidences of hypercholesterolemia and hypertriglyceridemia in infertile men [6]. Several studies have shown an association between obesity and high reactive oxygen species (ROS) production in sperm [8]. Semen of infertile men was found to have an increased ROS level, which was positively correlated with higher expressions of apoptotic mediators [9]. Inflammation is associated with oxidative stress owing to ROS or free-radical overproduction during the inflammatory reaction [10]

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