Timing Matters: Circadian Effects on Energy Homeostasis and Alzheimer’s Disease

• Published in: Trends in endocrinology and metabolism Vol. 30; no. 2; pp. 132 - 143
• Main Authors: Loehfelm, Aline, Boucsein, Alisa, Pretz, Dominik, Tups, Alexander
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01-02-2019
• Subjects: Alzheimer Disease - metabolism; Animals; diabetes; Diabetes Mellitus, Type 2 - metabolism; Energy Metabolism - physiology; Humans; hypothalamus; inflammation; insulin; leptin; signal transduction; Signal Transduction - physiology; insulin; signal transduction; inflammation; leptin; diabetes; hypothalamus
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/j.tem.2018.12.001

Metabolic syndrome and Alzheimer’s disease (AD) are two major health issues in modern society causing an extraordinary financial burden for the global healthcare systems. A tight link between the pathologies of obesity and type 2 diabetes (T2D), and more recently between T2D and AD, has been discovered. Furthermore, in recent years it has become apparent that the circadian clock has an important function in controlling metabolism. This review integrates the role of the circadian clock in the development of these metabolic derangements and vice versa. Common features such as central insulin resistance, altered glycogen synthase kinase 3β (GSK3β) signalling, and central inflammation are discussed, and therapeutic interventions targeting those mechanisms are mentioned briefly.
At the molecular level obesity, T2D and AD share common features such as central insulin resistance, chronic low-grade inflammation and altered GSK3β signalling.
Several antidiabetic drugs showed positive effects in AD patients, underpinning the molecular similarities of AD and T2D.
Recent studies have emphasised the circadian clock as an important player in whole-body energy metabolism. Circadian rhythms and clock gene expression are altered in states of metabolic derailment, and disruptions in circadian rhythms are associated with a number of different diseases including T2D and AD.
Considering the close relationship between circadian clocks and energy homeostasis, behavioural interventions, such as fasting regimens, to combat the consequences of disrupted rhythms and metabolism appear as a favourable tool.