Circadian regulators of intestinal lipid absorption

Abstract

Journal of Lipid Research Volume 56, 2015 761(MTP), to transport dietary and endogenous lipids, respectively ( 7-9 ). Therefore, it is possible that a major reason for the circadian regulation of plasma triglyceride depends on their assembly and secretion by the intestine and the liver. Circadian rhythms are centrally orchestrated by a set of clock genes expressed in the suprachiasmatic nuclei (SCN) of the brain. These genes are also expressed in other cells and their expression is entrained by various stimuli emanating from the SCN. Additionally, they are regulated by external stimuli such as food availability. Several intestinal functions, including lipid absorption, show diurnal variations. We will briefl y introduce clock genes and their regulation and intestinal lipid absorption, and then discuss three proteins that have been shown to be involved in the diurnal regulation of lipid absorption ( Fig. 1 ). LIGHT AND FOOD ENTRAINMENT OF CIRCADIAN RHYTHMSConstant periodicity of sunrise and sunset affects every organism. Some wake up with the sunrise while others go to sleep. However, wakefulness is always associated with physical activity aimed at gathering food. In contrast, sleep is associated with low locomotor activity and fasting. The information about the sunlight is transmitted from the eye via retino-hypothalamic neurons to bilateral SCN in the brain ( 10-12 ). These photic signals are deciphered in the SCN resulting in the increased expression of a clock gene, brain and muscle arylhydrocarbon receptor nuclear translocator ( Several behavioral and physiologic activities show circadian rhythms that are attuned to changes in light within a 24 h day. Plasma triacylglycerols exhibit diurnal variations in humans and rodents ( 1-6 ). Due to their hydrophobic nature, these lipids are transported in the plasma as major core constituents of apoB-containing lipoproteins. These lipoproteins are assembled in the endoplasmic reticulum and Golgi of enterocytes and hepatocytes with the assistance of a dedicated chaperone, microsomal triglyceride transfer protein Abbreviations: ARNT, arylhydrocarbon receptor nuclear translocator; Bmal1, brain and muscle ARNT -like protein 1; Clock, circadian locomotor output cycles kaput; CREBH, cAMP responsive element-binding protein H; Cry, cryptochrome; ER, endoplasmic reticulum; HNF, hepatic nuclear factor; MTP, microsomal triglyceride transfer protein; Per, period; PGC1 ␣ , PPAR ␥ coactivator 1-␣ ; Rev-erb ␣ , reverse erythroblastosis virus ␣ ; Ror ␣ , retinoic acid receptor-related orphan receptor ␣ ; SCN, suprachiasmatic nuclei; Shp, small heterodimer partner .

Circadian Clock, Time-Restricted Feeding and Reproduction

“…Animal model studies, particularly in the setting of obesity, diabetes, atherosclerosis, or other metabolism syndrome conditions by Clock genes, have led to an increase in recognition that a multitude of rhythmic functions, such as reproductive tissues in mammals, are controlled by molecular clockwork [5,13,15,48,85]. Clock/Clock mutant mice have differences in pregnancies, with a higher rate of fetal absorption, serious dystocia, morphological abnormalities, and lower serum progesterone and estradiol levels [24,86].…”

“…SCN's "circadian clock" genes can control behavior, feeding, and reproduction through neurotransmitters and hormones ( Figure 1) [2,8]. These circadian clock genes drive the body's circadian rhythm, and their disruption can lead to a host of issues such as cancer, obesity, and atherosclerosis [3,[9][10][11][12][13][14][15][16]. Disruption of the clock genes has also been implicated in a variety of malfunctions of homeostasis, including glucose, and lipid metabolism [17][18][19][20].…”

Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals

“…Intestinal epithelial cells exhibit rhythms in clock gene expression that are synchronized by SCN cues and the availability of food. Specifically, clock gene expression in the intestinal epithelial cells may control the rhythmic expression of different proteins involved in lipid absorption, such as MTP, apolipoprotein A IV and nocturnin (Hussain and Pan, 2014). Circadian oscillations of clock genes are not restricted only to the intestine, but can also be found in other regions and cell types of the gastrointestinal tract (Hoogerwerf et al, 2007;Pardini et al, 2005;Sladek et al, 2007).…”

New Insights into the Regulation of Chylomicron Production

“…Although ingested fat is the major driver of chylomicron production, recent research has shown that chylomicron production is a highly regulated process and that other factors affect this process, including nonlipid nutritional factors, hormones and circulating factors, genetic variants, circadian rhythms, nutraceuticals, and therapeutic interventions (pharmacological agents as well as bariatric surgery) (61,70,114,174) (Figure 3). These findings are important, as increased chylomicron production contributes to postprandial hypertriglyceridemia, an independent risk factor for atherosclerosis (8,111,174).…”

“…Per and Cry inhibit the expression of Clock and Bmal1 in an autoregulatory loop. Clock and Bmal1 heterodimers can also regulate the expression of other genes, including nuclear receptors such as RORα (RAR-related orphan receptor alpha) and RevErbα (70). Peripheral cells [outside of the central nervous system (CNS)] such as enterocytes also express Clock and Bmal1 with diurnal variation.…”