Correlation between ketones and mental fatigue in high fat‐induced obese and non‐obese rats

Obesity, often caused by a diet high in calories and low physical activity, may induce physical fatigue, as experienced via decreased locomotor activity and mental fatigue such as impaired cognition. This study aims to evaluate glucose and ketone levels secondary to high‐fat diet (HFD) exposure and signs of physical and mental fatigue. Fifty‐four 7‐week‐old male Sprague Dawley rats (Rattus norvegicus) were assigned to either an HFD (n = 28) or a standard diet (SD; n = 26) for a 6‐week period during which body weight, blood glucose, and ketones were measured twice per week. An open field (OF) paradigm was used to measure locomotor activity, while novel object recognition (NOR) test was used as an indicator of cognition. Animals in the HFD group weighed more than SD rats (8.4 g; p < 0.05) starting at Day 11, blood glucose levels were higher in the HFD group versus SD rats (3.9 mg/dl; p < 0.05) beginning in Week 5, and ketones were lower for the HFD versus the SD group throughout the study (0.34 mmol/L on average; p < 0.05). Although there was no significant difference in locomotor activity between the HFD and SD groups (p = 0.12), regardless of diet, higher ketone levels were associated with increased NOR time and ratio between the familiar and novel objects (p < 0.01). Thus, this study provides evidence that an increased level of ketones is associated with greater cognitive performance and a lesser probability of experiencing mental fatigue.