Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− mice

Abstract Objective An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E...

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Main Authors: Anthony Juritsch, Yi-Ting Tsai, Mulchand S. Patel, Todd C. Rideout
Format: Article
Language:English
Published: BMC 2017-10-01
Series:BMC Research Notes
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13104-017-2859-3
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author Anthony Juritsch
Yi-Ting Tsai
Mulchand S. Patel
Todd C. Rideout
author_facet Anthony Juritsch
Yi-Ting Tsai
Mulchand S. Patel
Todd C. Rideout
author_sort Anthony Juritsch
collection DOAJ
description Abstract Objective An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E deficient offspring from dams fed a chow diet supplemented with cholesterol (0.15%, CH) or cholesterol and PS (2%) (CH/PS) throughout pregnancy and lactation. Results Serum lipid concentrations and lipoprotein particle numbers were exacerbated in offspring from cholesterol-supplemented mothers but normalized to chow-fed levels in pups exposed to PS through the maternal diet during gestation and lactation. Compared with the CH pups, pups from PS-supplemented mothers demonstrated higher (p < 0.05) expression of the primary intestinal cholesterol transport protein (Niemann-Pick C1-like 1) and the rate-limiting enzyme in hepatic cholesterol synthesis (HMG-CoAr), suggestive of a compensatory response to restore cholesterol balance. Furthermore, pups from PS-supplemented mothers exhibited a coordinated downregulation (p < 0.05) of several genes regulating fatty acid synthesis including PGC1β, SREBP1c, FAS, and ACC compared with the CH group. These results suggest that maternal PS supplementation during hypercholesterolemic pregnancies protects against aberrant lipid responses in newly-weaned offspring and results in differential regulation of cholesterol and lipid regulatory targets within the enterohepatic loop.
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spelling doaj.art-0c5e002a08f545d497b5b4833c70a1752022-12-21T21:58:14ZengBMCBMC Research Notes1756-05002017-10-011011710.1186/s13104-017-2859-3Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− miceAnthony Juritsch0Yi-Ting Tsai1Mulchand S. Patel2Todd C. Rideout3Departments of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at BuffaloDepartments of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at BuffaloBiochemistry, Jacobs School of Medicine and Biomedical Sciences, University at BuffaloDepartments of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at BuffaloAbstract Objective An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E deficient offspring from dams fed a chow diet supplemented with cholesterol (0.15%, CH) or cholesterol and PS (2%) (CH/PS) throughout pregnancy and lactation. Results Serum lipid concentrations and lipoprotein particle numbers were exacerbated in offspring from cholesterol-supplemented mothers but normalized to chow-fed levels in pups exposed to PS through the maternal diet during gestation and lactation. Compared with the CH pups, pups from PS-supplemented mothers demonstrated higher (p < 0.05) expression of the primary intestinal cholesterol transport protein (Niemann-Pick C1-like 1) and the rate-limiting enzyme in hepatic cholesterol synthesis (HMG-CoAr), suggestive of a compensatory response to restore cholesterol balance. Furthermore, pups from PS-supplemented mothers exhibited a coordinated downregulation (p < 0.05) of several genes regulating fatty acid synthesis including PGC1β, SREBP1c, FAS, and ACC compared with the CH group. These results suggest that maternal PS supplementation during hypercholesterolemic pregnancies protects against aberrant lipid responses in newly-weaned offspring and results in differential regulation of cholesterol and lipid regulatory targets within the enterohepatic loop.http://link.springer.com/article/10.1186/s13104-017-2859-3Maternal hypercholesterolemiaOffspringPhytosterolsLiverIntestinemRNA
spellingShingle Anthony Juritsch
Yi-Ting Tsai
Mulchand S. Patel
Todd C. Rideout
Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− mice
BMC Research Notes
Maternal hypercholesterolemia
Offspring
Phytosterols
Liver
Intestine
mRNA
title Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− mice
title_full Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− mice
title_fullStr Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− mice
title_full_unstemmed Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− mice
title_short Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE−/− mice
title_sort transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoe mice
topic Maternal hypercholesterolemia
Offspring
Phytosterols
Liver
Intestine
mRNA
url http://link.springer.com/article/10.1186/s13104-017-2859-3
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