Circadian regulation of metabolic homeostasis: causes and consequences

Abstract

Robust circadian rhythms in metabolic processes have been described in both humans and animal models, at the whole body, individual organ, and even cellular level. Classically, these time-of-day-dependent rhythms have been considered secondary to fluctuations in energy/nutrient supply/demand associated with feeding/fasting and wake/sleep cycles. Renewed interest in this field has been fueled by studies revealing that these rhythms are driven, at least in part, by intrinsic mechanisms and that disruption of metabolic synchrony invariably increases the risk of cardiometabolic disease. The objectives of this paper are to provide a comprehensive review regarding rhythms in glucose, lipid, and protein/amino acid metabolism, the relative influence of extrinsic (eg, neurohumoral factors) versus intrinsic (eg, cell autonomous circadian clocks) mediators, the physiologic roles of these rhythms in terms of daily fluctuations in nutrient availability and activity status, as well as the pathologic consequences of dyssynchrony.

Keywords: circadian clocks; circadian rhythm; dyssynchrony; metabolic homeostasis; neurohumoral factors; time-of-day-dependent rhythms.

Figure 1

Measures and mediators of metabolic flux. Abbreviations: SUMO, sumoylation; Ub, ubiquitination; GlcNAc, O-linked N-acetylglucosamine; P, phosphorylation.

Figure 2

Time-of-day-dependent rhythms in glucose, lipid, and protein/amino acid metabolism in rodent models. Abbreviation: NEFAs, nonesterified fatty acids.