Abstract:
Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation.
In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy.
In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure.
In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well.
There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.
Source: Lacourt TE, Vichaya EG, Chiu GS, Dantzer R, Heijnen CJ. The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Front Behav Neurosci. 2018 Apr 26;12:78. doi: 10.3389/fnbeh.2018.00078. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932180/ (Full article)