The high costs of low-grade inflammation: persistent fatigue as a consequence of reduced cellular-energy availability and nonadaptive energy expenditure
- 1University of Texas MD Anderson Cancer Center, United States
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 nonadaptive 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.
Keywords: Cytokines, Metabolism, effort, Motivation, energy balance, chronic fatigue syndrome, Cancer-related fatigue
Received: 20 Dec 2017;
Accepted: 09 Apr 2018.
Edited by:Martin Hadamitzky, Universitätsklinikum Essen, Germany
Reviewed by:Andrew Chan, Ruhr University Bochum, Germany
Alessandro Laviano, Sapienza Università di Roma, Italy
Lisa Mullen, Brighton and Sussex Medical School, University of Sussex, United Kingdom
Copyright: © 2018 Lacourt, Vichaya, Chiu, Dantzer and Heijnen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: PhD. Tamara Lacourt, University of Texas MD Anderson Cancer Center, Houston, United States, firstname.lastname@example.org