Lipid metabolism around the body clocks

Abstract

Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid metabolism are responsible for the development of various pathologies comprising metabolic syndrome, obesity, and type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative in most cells of our body, coordinate temporal aspects of lipid homeostasis. In this review we summarize current knowledge on the circadian regulation of lipid digestion, absorption, transportation, biosynthesis, catabolism, and storage. Specifically, we focus on the molecular interactions between functional clockwork and biosynthetic pathways of major lipid classes comprising cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, and sphingomyelins. A growing body of epidemiological studies associate a socially imposed circadian misalignment common in modern society with growing incidence of metabolic disorders, however the disruption of lipid metabolism rhythms in this connection has only been recently revealed. Here, we highlight recent studies that unravel the mechanistic link between intracellular molecular clocks, lipid homeostasis and development of metabolic diseases based on animal models of clock disruption and on innovative translational studies in humans. We also discuss the perspectives of manipulating circadian oscillators as a potentially powerful approach for preventing and managing metabolic disorders in human patients.

Keywords: Circadian clocks; circadian lipidomics; lipid metabolism; metabolic diseases; tissue-specific circadian regulation; type 2 diabetes.