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ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production.

ABSTRACT: The uptake of dietary lipids from the small intestine is a complex process that depends on the activities of specific membrane receptors with yet unknown regulatory mechanisms. Using both mouse models and human cell lines, we show here that intestinal lipid absorption by the scavenger receptor class B type 1 (SR-BI) is subject to control by retinoid signaling. Retinoic acid via retinoic acid receptors induced expression of the intestinal transcription factor ISX. ISX then repressed the expression of SR-B1 and the carotenoid-15,15'-oxygenase Bcmo1. BCMO1 acts downstream of SR-BI and converts absorbed beta,beta-carotene to the retinoic acid precursor, retinaldehyde. Using BCMO1-knockout mice, we demonstrated increased intestinal SR-BI expression and systemic beta,beta-carotene accumulation. SR-BI-dependent accumulation of beta,beta-carotene was prevented by dietary retinoids that induced ISX expression. Thus, our study revealed a diet-responsive regulatory network that controls beta,beta-carotene absorption and vitamin A production by negative feedback regulation. The role of SR-BI in the intestinal absorption of other dietary lipids, including cholesterol, fatty acids, and tocopherols, implicates retinoid signaling in the regulation of lipid absorption more generally and has clinical implications for diseases associated with dyslipidemia.

SUBMITTER: Lobo GP

PROVIDER: S-EPMC2874479 | biostudies-other | 2010 Jun

REPOSITORIES: biostudies-other

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ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production.

Lobo Glenn P GP Hessel Susanne S Eichinger Anne A Noy Noa N Moise Alexander R AR Wyss Adrian A Palczewski Krzysztof K von Lintig Johannes J

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20100108 6

The uptake of dietary lipids from the small intestine is a complex process that depends on the activities of specific membrane receptors with yet unknown regulatory mechanisms. Using both mouse models and human cell lines, we show here that intestinal lipid absorption by the scavenger receptor class B type 1 (SR-BI) is subject to control by retinoid signaling. Retinoic acid via retinoic acid receptors induced expression of the intestinal transcription factor ISX. ISX then repressed the expressio ...[more]

PMID: 20061533

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Project description:Finishing pigs (N = 224; 28.66 ± 1.90 kg bodyweight) were randomly assigned across 56 pens of either four barrows or gilts, and assigned to one of four diets: control (7,656 IU vitamin A/kg), control supplemented with vitamin A (4.36 ppm, Rovimix A 1000, DSM, Parsippany, NJ, USA), control supplemented with beta-carotene (163.28 ppm, Rovimix β-Carotene 10%, DSM, Parsippany), or control supplemented with oxidized beta-carotene (40 ppm; 10% active ingredient, Avivagen, Ottawa, ON, Canada). Pigs and feeder weights were obtained at the start of the study (d 0), and end of each phase (d 21, 42, and 63). A subset of gilts had a blood sample taken via jugular venipuncture on d 0, a blood sample and vaccinations of Lawsonia intracellularis and porcine circovirus type 2 (PCV2) on d 18, a blood sample and booster vaccination of PCV2 on d 39, a blood sample on day 60, and a final blood sample on day 63. Gilts were euthanized at the end of the study to obtain a liver (entire right lobe) and a jejunum sample (15.24 cm at 10% of length). Additionally, the second and fourth right anterior mammary were collected to assess anterior mammary tissues. Data were analyzed in SAS 9.4 (Statistical Analysis System, Cary, NC) via GLIMMIX procedure. Oxidized beta-carotene supplementation increased (P = 0.02) ADG across phases over vitamin A supplementation, although there were no differences (P = 0.18) in the body weight of pigs. There was no effect (P > 0.05) of diet on plasma or hepatic retinol, IgG or IgM levels, or immune cell presence in developing mammary tissue. Supplemented vitamin A tended (P = 0.05) to increase the mRNA abundance of retinol binding protein in the jejunum, but other mRNA abundance for genes (alcohol dehydrogenase class 1, lecithin retinol acyltransferase phosphatidylcholine-retinol O-acyltransferase, and beta-carotene oxygenase 1) were not affected (P > 0.05) by dietary treatments. A diet by time interaction (P = 0.04) was noted for the circovirus S/P ratio, where vitamin A supplementation had the best ratio compared to other diets. Analyzed titer levels for the circovirus vaccine had an interaction (P < 0.01) for diet by time, where vitamin A supplementation had the highest titer at the end of the study. Thus, pigs supplemented with oxidized beta-carotene had an improved ADG over vitamin A supplemented pigs, but pigs supplemented with vitamin A seemed to have an improved immune status.

Dataset Information

ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production.

Publications

ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production.

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