TY - JOUR
T1 - The high costs of low-grade inflammation
T2 - Persistent fatigue as a consequence of reduced cellular-energy availability and non-adaptive energy expenditure
AU - Lacourt, Tamara E.
AU - Vichaya, Elisabeth G.
AU - Chiu, Gabriel S.
AU - Dantzer, Robert
AU - Heijnen, Cobi J.
N1 - Funding Information:
This work was supported by RO1NS073939, RO1CA193522, and RO1CA208371 from the National Institutes of Health, USA.
Publisher Copyright:
© 2018 Lacourt, Vichaya, Chiu, Dantzer and Heijnen.
PY - 2018/4/26
Y1 - 2018/4/26
N2 - 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.
AB - 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.
KW - Cancer-related fatigue
KW - Chronic fatigue syndrome
KW - Cytokines
KW - Effort
KW - Energy balance
KW - Metabolism
KW - Motivation
UR - http://www.scopus.com/inward/record.url?scp=85046680745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046680745&partnerID=8YFLogxK
U2 - 10.3389/fnbeh.2018.00078
DO - 10.3389/fnbeh.2018.00078
M3 - Review article
C2 - 29755330
AN - SCOPUS:85046680745
SN - 1662-5153
VL - 12
JO - Frontiers in Behavioral Neuroscience
JF - Frontiers in Behavioral Neuroscience
M1 - 78
ER -