Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism

Abstract

Disorders of lipid and lipoprotein metabolism and transport are responsible for the development of a large spectrum of pathologies, ranging from cardiovascular diseases, to metabolic syndrome, even to tumour development. Recently, a deeper knowledge of the molecular mechanisms that control our biological clock and circadian rhythms has been achieved. From these studies it has clearly emerged how the molecular clock tightly regulates every aspect of our lives, including our metabolism. This review analyses the organisation and functioning of the circadian clock and its relevance in the regulation of physiological processes. We also describe metabolism and transport of lipids and lipoproteins as an essential aspect for our health, and we will focus on how the circadian clock and lipid metabolism are greatly interconnected. Finally, we discuss how a deeper knowledge of this relationship might be useful to improve the recent spread of metabolic diseases.

Figure 1

Schematic drawing representing the molecular machine that regulates the circadian clock and its interplay with metabolism. Waves symbolises circadian regulation. NAMPT: nicotinamide phosphoribosyltransferase. See text for details.

Figure 2

Schematic overview of the interplay between the central and peripheral circadian clocks. Waves symbolises circadian regulation. RHT: retinohypothalamic tract; SCN: suprachiasmatic nucleus; sPVZ: subparaventricular zone; POA: preoptic area; BNST: bed nucleus of the stria terminalis; ARC: arcuate nucleus; DMH: dorsomedial hypothalamus; PVN: paraventricular nucleus; ACTH: adrenocorticotropic hormone; HMGCoAR: HMG-CoA Reductase; FAS: Fatty Acid Synthase; ACC: acetyl-CoA carboxylase; ApoAIV: apolipoprotein AIV; FABP4: fatty-acid-binding-protein 4; CYP7A1: cholesterol-7α-hydroxylase; DGAT2: diacylglycerol acyltransferase 2; MTP: microsomal triglyceride transfer protein; SCD-1: stearoyl-CoA desaturase-1; NPC1L1: Niemann-Pick C1-like 1. See text for details.

Figure 3

Schematic view of the tight association between circadian rhythms, metabolism and hormonal homeostasis in humans. Waves symbolises circadian regulation. See text for details.