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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M900085-JLR200 on April 22, 2009

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Journal of Lipid Research, Vol. 50, 1800-1813, September 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Clock is important for food and circadian regulation of macronutrient absorption in mice

Xiaoyue Pan and M. Mahmood Hussain

Departments of Anatomy and Cell Biology, and Pediatrics, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203

1 To whom correspondence should be addressed. e-mail: mahmood.hussain{at}downstate.edu

Clock genes respond to external stimuli and exhibit circadian rhythms. This study investigated the expression of clock genes in the small intestine and their contribution in the regulation of nutrient absorption by enterocytes. We examined expression of clock genes and macronutrient transport proteins in the small intestines of wild-type and Clock mutant (Clkmt/mt) mice with free or limited access to food. In addition, we studied absorption of macronutrients in these mice. Intestinal clock genes show circadian expression and respond to food entrainment in wild-type mice. Dominant negative Clock in Clkmt/mt mice disrupts circadian expression and food entrainment of clock genes. The absorption of lipids and monosaccharides was high in Clkmt/mt mice whereas peptide absorption was reduced. Molecular studies revealed that Clock regulates several transport proteins involved in nutrient absorption. Clock plays an important role in light and food entrainment of intestinal functions by regulating nutrient transport proteins. Disruptions in intestinal circadian activity may contribute to hyperlipidemia and hyperglycemia.

Supplementary key words lipid absorption • lipoprotein assembly • cholesteryl esters • triacylglycerol • microsomal triglyceride transfer protein • intestine • gene transcription • Clock controlled genes

Abbreviations: {alpha}MG, {alpha}-methyl-glucopyranoside; apo, apolipoprotein; BBMV, brush border membrane vesicle; Clkmt/mt, Clock mutant; FEO, food-entrained oscillator; Dgat, diacylglycerol acyltransferase; GLUT, glucose transporter; gly-sar, glycyl-sarcosine; LD, light/dark; LEO, light-entrained oscillator; MGAT, monoacylglycerol acyltransferase; MTP, microsomal triglyceride transfer protein; PEPT1, proton-coupledoligopeptide transporter 1; SCN, suprachiasmatic nuclei; SGLT1, Na+/glucose cotransporter 1; SR-B, scavenger receptor-B; WT, wild type


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