Intestinal clock modulates rhythmic hepatic metabolism.

The circadian clocks control daily rhythms of molecular and cellular processes, leading to variations in physiology and behavior. [1] Reppert S.M. Weaver D.R. Coordination of circadian timing in mammals. Nature. 2002; 418: 935-941 Crossref PubMed Scopus (3422) Google Scholar In mammals, energy metabolism is intimately linked to the circadian system. [2] Asher G. Schibler U. Crosstalk between Components of Circadian and Metabolic Cycles in Mammals. Cell Metabolism. 2011; 13: 125-137 Abstract Full Text Full Text PDF PubMed Scopus (470) Google Scholar This is reflected at the molecular level, with most metabolic genes and metabolites oscillating in a circadian manner. [3] Dallmann R. Viola A.U. Tarokh L. Cajochen C. Brown S.A. The human circadian metabolome. Proc Natl Acad Sci U S A. 2012; 109: 2625-2629 Crossref PubMed Scopus (410) Google Scholar Functionally, the clock of the suprachiasmatic nucleus of the brain orchestrates the clocks in other parts of the body. A much less characterized hierarchy also exists between organs in the periphery, with the liver positioned in the high-level rank. [4] Manella G. Sabath E. Aviram R. Dandavate V. Ezagouri S. Golik M. et al. The liver-clock coordinates rhythmicity of peripheral tissues in response to feeding. Nature Metabolism. 2021; 3: 829-842 Crossref PubMed Scopus (39) Google Scholar Features of the metabolic syndrome, such as obesity, diabetes, and hypertension are related to circadian misalignment, [5] Han H. Dou J. Hou Q. Wang H. Role of Circadian Rhythm and Impact of Circadian Rhythm Disturbance on the Metabolism and Disease. J Cardiovasc Pharmacol. 2022; 79: 254-263 Crossref PubMed Scopus (5) Google Scholar and the implementation of time-restricted feeding strategies to resynchronize the clocks has shown consistent benefits to manage metabolic diseases. [6] Sutton E.F. Beyl R. Early K.S. Cefalu W.T. Ravussin E. Peterson C.M. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metab. 2018; 27: 1212-1221.e1213 Abstract Full Text Full Text PDF PubMed Scopus (651) Google Scholar In the intestine, nutrient processing and absorption follow a temporal pattern coordinated by the local clock. [7] Hussain M.M. Pan X. Circadian Regulation of Macronutrient Absorption. J Biol Rhythms. 2015; 30: 459-469 Crossref PubMed Scopus (30) Google Scholar The intestine is anatomically connected to the liver via the portal vein and has a profound impact on hepatic function and metabolic deregulation. [8] Albillos A. de Gottardi A. Rescigno M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol. 2020; 72: 558-577 Abstract Full Text Full Text PDF PubMed Scopus (579) Google Scholar Curiously, there is not much information on the potential role of the intestinal-liver circuit in the modulation of liver rhythmicity and metabolism. Reprogramming of rhythmic liver metabolism by intestinal clockJournal of HepatologyPreviewTemporal oscillations in intestinal nutrient processing and absorption are coordinated by the local clock, which leads to the hypothesis that intestine clock has major impact on shaping peripheral rhythms via diurnal nutritional signals. Here we investigate the role of intestine clock in controlling liver rhythmicity and metabolism. Full-Text PDF