Comparison of Intermittent Fasting and Voluntary Wheel Running on Mental and Physical Fatigue in High‐Fat‐induced Obese and Non‐obese Rats

Abstract

Obesity has affected an alarming 42% of the American population, making dietary modification and weight loss methods a hot topic in combating this illness and its many complications. Physical exercise has long been recognized as treatment for obesity as it results in weight loss and improved glycemic control. Yet another method that has gained recent attention for its health benefits is the intermittent fasting (IF) regimen, though IF has had its place in many religions for centuries. Exercise and IF are also associated with improvements in mental health, including combating mental illness like depression and improving memory. However, the mechanism behind how these regimens exert these benefits remains to be elucidated. Additionally, the possibility for mental and physical fatigue while on these regimens has not been readily assessed in the obese population. To evaluate mental and physical fatigue and better understand the underlying mechanisms resulting in the stated benefits, 32 male Sprague Dawley rats were obtained at 7‐weeks of age and subjected to diet‐induced obesity via ad libitumfeeding of a high‐fat diet (HFD; 60% kcal fat; D12492 from Research Diets Inc) or a standard diet with matched sucrose levels (SD; 10% kcal fat; D12450J from Research Diets Inc) for 8 weeks, after which behavioral testing was performed for an additional two weeks. Behavioral testing included 8 trials of open field test to assess physical fatigue, and 4 intervals of novel object recognition test to assess mental fatigue. Once completed, rats from the HFD‐fed, now referred to as obese, and SD‐fed groups were subjected to either IF (18 hour daily fast, 6‐hour daily feeding), voluntary wheel running (VWR; rodent paradigm for human exercise), or control conditions for 3 weeks. After the 3‐week period, rats underwent the same 2‐week behavioral testing routine as previously mentioned. Obese rats weighed significantly more than SD‐fed rats (p<0.05) and exhibited higher ketone levels (p < 0.05). Behavioral testing did not indicate changes in mental or physical fatigue. Blood glucose levels were lowered by VWR in both obese and SD groups compared to controls (p<0.05), while IF led to lower glucose levels in both obese and SD groups compared to VWR and controls (p<0.05). In both obese and SD groups, VWR resulted in higher ketone levels compared to controls (p<0.05), while IF ketone levels were higher than both VWR and control rats (p<0.05). Behavioral testing results demonstrated that IF and VWR did not contribute to mental or physical fatigue in either obese or SD‐fed groups. However, in both obese and SD‐fed groups, IF resulted in a greater distance traveled during open field testing when compared to VWR (p<0.05), indirectly indicating an increased resistance to physical fatigue in IF rats. Together, these results support the use of IF and VWR in both obese and SD‐fed individuals as a strategy for mitigating the negative effects of obesity. Given the elevated ketone levels in both IF and VWR rats, this study demonstrates that ketone levels may contribute to the benefits of these regimens.