Circadian Rhythms and the Gastrointestinal Tract: Relationship to Metabolism and Gut Hormones

Abstract

Abstract Circadian rhythms are 24-hour biological rhythms within organisms that have developed over evolutionary time due to predefined environmental changes, mainly the light-dark cycle. Interestingly, metabolic tissues, which are largely responsible for establishing diurnal metabolic homeostasis, have been found to express cell-autonomous clocks that are entrained by food intake. Disruption of the circadian system, as seen in individuals who conduct shift work, confers significant risk for the development of metabolic diseases such as type 2 diabetes and obesity. The gastrointestinal (GI) tract is the first point of contact for ingested nutrients and is thus an essential organ system for metabolic control. This review will focus on the circadian function of the GI tract with a particular emphasis on its role in metabolism through regulation of gut hormone release. First, the circadian molecular clock as well as the organization of the mammalian circadian system is introduced. Next, a brief overview of the structure of the gut as well as the circadian regulation of key functions important in establishing metabolic homeostasis is discussed. Particularly, the focus of the review is centered around secretion of gut hormones; however, other functions of the gut such as barrier integrity and intestinal immunity, as well as digestion and absorption, all of which have relevance to metabolic control will be considered. Finally, we provide insight into the effects of circadian disruption on GI function and discuss chronotherapeutic intervention strategies for mitigating associated metabolic dysfunction.