Regulation of Intestinal Lipid Absorption by Clock Genes

Hussain, M. Mahmood

doi:10.1146/annurev-nutr-071813-105322

Cited by 26 publications

(33 citation statements)

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“…Various functions of the intestine, such as motility, gastric emptying, DNA synthesis, epithelial cell renewal, food anticipatory activity, and nutrient absorption, exhibit circadian rhythms ( 14,20,(27)(28)(29). It is well-known that the major complaints in shift workers and transcontinental travelers are related to gastrointestinal disturbances ( 30 ).…”

Section: Expression Of Clock Genes In the Intestinementioning

confidence: 99%

“…Intestinal lipid absorption involves hydrolysis of dietary fat in the intestinal lumen, uptake of hydrolyzed products by the enterocytes, resynthesis of lipids, and assembly and secretion of chylomicrons. Several reviews have extensively discussed these steps in lipid absorption ( 7,8,14,20,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). Because lipids are water-insoluble, an important step in the digestion of these lipids is their emulsifi cation with bile salts ( 39,43 ).…”

Section: Circadian Regulation Of Intestinal Lipid Absorptionmentioning

confidence: 99%

“…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 etc.) cues (14)(15)(16)(17)(18)(19)(20). Therefore, diurnal regulation of peripheral tissues, such as the intestine, is affected by several central, hormonal, and environmental stimuli.…”

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confidence: 99%

“…Food is a potent synchronizer of peripheral clocks and entrains various behavioral and physiologic activities (14)(15)(16)(20)(21)(22)(23)(24)(25). This can be easily demonstrated by providing food for a few days in the daytime to rodents that usually consume their meal in the nighttime with no disruptions in the light on/off schedule.…”

mentioning

confidence: 99%

“…However, the clock genes involved in the lightinduced oscillators may participate in the food-entrainment response. It is likely that the food-entrained oscillator is a network of several neural sites in the brain that cooperate to elicit a behavioral and physiologic response ( 20,26 ).…”

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Circadian regulators of intestinal lipid absorption

Hussain

Pan

2015

Journal of Lipid Research

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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 .

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Section: Expression Of Clock Genes In the Intestinementioning

confidence: 99%

Section: Circadian Regulation Of Intestinal Lipid Absorptionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Circadian regulators of intestinal lipid absorption

Hussain

Pan

2015

Journal of Lipid Research

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Bmal1 regulates production of larger lipoproteins by modulating cAMP‐responsive element‐binding protein H and apolipoprotein AIV

Pan

Hussain

2021

Hepatology

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Background and Aims: High plasma lipid/lipoprotein levels are risk factors for various metabolic diseases. We previously showed that circadian rhythms regulate plasma lipids and deregulation of these rhythms causes hyperlipidemia and atherosclerosis in mice. Here, we show that global and liver-specific brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1)-deficient mice maintained on a chow or Western diet developed hyperlipidemia, denoted by the presence of higher amounts of triglyceride-rich and apolipoprotein AIV (ApoAIV)-rich larger chylomicron and VLDL due to overproduction. Approach and Results: Bmal1 deficiency decreased small heterodimer partner (Shp) and increased microsomal triglyceride transfer protein (MTP), a key protein that facilitates primordial lipoprotein assembly and secretion. Moreover, we show that Bmal1 regulates cAMP-responsive element-binding protein H (Crebh) to modulate ApoAIV expression and the assembly of larger lipoproteins. This is supported by the observation that Crebh-deficient and ApoAIV-deficient mice, along with Bmal1-deficient mice with knockdown of Crebh, had smaller lipoproteins. Further, overexpression of Bmal1 in Crebhdeficient mice had no effect on ApoAIV expression and lipoprotein size. Conclusions: These studies indicate that regulation of ApoAIV and assembly of larger lipoproteins by Bmal1 requires Crebh. Mechanistic studies showed that Bmal1 regulates Crebh expression by two mechanisms. First, Bmal1 interacts with the Crebh promoter to control circadian regulation. Second, Bmal1 increases Rev-erbα expression, and nuclear receptor subfamily 1 group D member 1 (Nr1D1, Rev-erbα) interacts with the Crebh promoter to repress expression. In short, Bmal1 modulates both the synthesis of primordial lipoproteins and their subsequent expansion into larger lipoproteins by regulating two different proteins, MTP and ApoAIV, through two different

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Time after time: circadian clock regulation of intestinal stem cells

Parasram

Karpowicz

2019

Cell. Mol. Life Sci.

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Regulation of Intestinal Lipid Absorption by Clock Genes

Cited by 26 publications

References 73 publications

Circadian regulators of intestinal lipid absorption

Circadian regulators of intestinal lipid absorption

Bmal1 regulates production of larger lipoproteins by modulating cAMP‐responsive element‐binding protein H and apolipoprotein AIV

Time after time: circadian clock regulation of intestinal stem cells

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