Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 May;20(4):177-85.
doi: 10.1016/j.tem.2009.01.001. Epub 2009 Apr 6.

Clock genes, intestinal transport and plasma lipid homeostasis

M Mahmood Hussain  1 , Xiaoyue Pan
Affiliations
Review

Clock genes, intestinal transport and plasma lipid homeostasis

M Mahmood Hussain et al. Trends Endocrinol Metab. 2009 May.

Abstract

Light and food are two major environmental factors that impact daily life. Light entrainment is centrally controlled by suprachiasmatic nuclei of the hypothalamus. Food entrainment might require cooperation between the intestine and dorsomedial hypothalamus. Clock genes that are essential for light entrainment also play a part in food entrainment. Understanding the role of clock genes in the entrainment of intestinal functions, as well as in gut-brain communication during food entrainment, will enhance our understanding of gastrointestinal and metabolic disorders. This review highlights recent studies examining light- and food-entrained regulation of plasma lipids and of various intestinal activities and offers insight into the role of the intestine in food entrainment.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Light and food entrainment. (a) Light entrainment. Light is sensed by the retina, and this information is transmitted via the retino-hypothalamic tract to the suprachiasmatic nuclei (SCN) in the brain (LEO). This information elicits changes in the expression of various transcription factors that constitute the clock genes. Circadian regulation in the SCN is crucially dependent on two transcription factors, Clock and Bmal1. Clock and Bmal1 heterodimers activate three Per and two Cry genes, which heterodimerize to negatively regulate Clock/Bmal1 activity. Other peripheral tissues also express clock genes, and their circadian behavior is entrained by cues originating from the SCN. (b) Food entrainment. Availability of food at a given time with regular periodicity is also a strong cue to entrain different physiological and behavioral activities. It is likely that the intestine plays a crucial part in food entrainment. The intestine might send signals to entrain the dorsomedial hypothalamus about the availability of food (FEO). The dorsomedial hypothalamus, in turn, might send signals to other tissues to entrain various behavioral and physiologic functions associated with food anticipation, digestion and absorption.
Figure 2
Figure 2
Clock genes and diurnal regulation. Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2, Rev-erbα and Rorα constitute core clock genes. Clock/Bmal1 heterodimers interact with promoter sequences in different genes to increase their transcription and represent a major feed-forward loop. Per and Cry protein heterodimers oppose their action to act as repressors and constitute a major negative feedback loop. Activator Rorα, possibly along with a co-activator (Pgc-1α), and repressor Rev-erbα regulate Bmal1 expression, constituting secondary positive and negative feedback loops, respectively. Different colors are used to represent individual transcription factors.
Figure 3
Figure 3
Clock-controlled genes and regulation of metabolic functions. Clock/Bmal1 heterodimers bind to E-boxes to increase expression of genes independent of the classical feedback loop of clock genes. These genes are referred to as ‘clock-controlled genes’. Induction of these clock-controlled genes helps propagate circadian signals via regulation of different metabolic genes leading to various physiological and behavioral outputs. For example, Pparα upregulates genes involved in fatty acid oxidation, and Rev-erbα suppresses genes involved in bile acid metabolism. Similarly, albumin D-site-binding protein (Dpb) and arginine vasopressin (Avp) have been shown to regulate genes involved in drug metabolism and blood pressure control, respectively. These clock-controlled genes modulate more than one physiologic activity; therefore, interactions among these clock-controlled genes might be important in regulating cellular and biochemical functions. This figure is intended to introduce the concept and is not comprehensive.
Figure I
Figure I
The endogenous and exogenous pathways ensure complete utilization of fat as an energy source. (a) Exogenous pathway. Absorption of dietary and biliary lipids by the intestines and their catabolism in the plasma. (b) Endogenous pathway. Liver mobilizes the delivered and newly synthesized fat.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lowrey PL, Takahashi JS. Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet. 2004;5:407–441. - PMC - PubMed
    1. Hastings MH, et al. A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci. 2003;4:649–661. - PubMed
    1. Green CB, et al. The meter of metabolism. Cell. 2008;134:728–742. - PMC - PubMed
    1. Takahashi JS, et al. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet. 2008;9:764–775. - PMC - PubMed
    1. Levi F, Schibler U. Circadian rhythms: mechanisms and therapeutic implications. Annu Rev Pharmacol Toxicol. 2007;47:593–628. - PubMed

Publication types