Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S]
The investigation of the human disease sitosterolemia (MIM 210250) has shed light not only on the pathways by which dietary sterols may traffic but also on how the mammalian body rids itself of cholesterol and defends against xenosterols. Two genes, ABCG5 and ABCG8, located at the sitosterolemia loc...
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doaj-89c12fcca52d476e88789229e590c4152021-04-28T06:07:31ZengElsevierJournal of Lipid Research0022-22752013-02-01542397409Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S]Curzio Solca0G. Stephen Tint1Shailendra B. Patel2Clement J. Zablocki Veterans Medical Health Center, Milwaukee, WI; Division of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, WIDepartment of Veterans Affairs, New Jersey Health Care System, East Orange, NJ; New Jersey Medical School,* University of Medicine and Dentistry of New Jersey, Newark, NJTo whom correspondence should be addressed sbpatel@mcw.edu; Clement J. Zablocki Veterans Medical Health Center, Milwaukee, WI; Division of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, WI; To whom correspondence should be addressed sbpatel@mcw.eduThe investigation of the human disease sitosterolemia (MIM 210250) has shed light not only on the pathways by which dietary sterols may traffic but also on how the mammalian body rids itself of cholesterol and defends against xenosterols. Two genes, ABCG5 and ABCG8, located at the sitosterolemia locus, each encodes a membrane-bound ABC half-transporter and constitutes a functional unit whose activity has now been shown to account for biliary and intestinal sterol excretion. Knockout mice deficient in Abcg5 or Abcg8 recapitulate many of the phenotypic features of sitosterolemia. During the course of our studies to characterize these knockout mice, we noted that these mice, raised on normal rodent chow, exhibited infertility as well as loss of abdominal fat. We show that, although sitosterolemia does not lead to any structural defects or to any overt endocrine defects, fertility could be restored if xenosterols are specifically blocked from entry and that the loss of fat is also reversed by a variety of maneuvers that limit xenosterol accumulation. These studies show that xenosterols may have a significant biological impact on normal mammalian physiology and that the Abcg5 or Abcg8 knockout mouse model may prove useful in investigating the role of xenosterols on mammalian physiology.http://www.sciencedirect.com/science/article/pii/S0022227520428056Abcg8Abcg5phytosterolsadipocytesinfertilityezetimibe |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Curzio Solca G. Stephen Tint Shailendra B. Patel |
spellingShingle |
Curzio Solca G. Stephen Tint Shailendra B. Patel Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S] Journal of Lipid Research Abcg8 Abcg5 phytosterols adipocytes infertility ezetimibe |
author_facet |
Curzio Solca G. Stephen Tint Shailendra B. Patel |
author_sort |
Curzio Solca |
title |
Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S] |
title_short |
Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S] |
title_full |
Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S] |
title_fullStr |
Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S] |
title_full_unstemmed |
Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[S] |
title_sort |
dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2013-02-01 |
description |
The investigation of the human disease sitosterolemia (MIM 210250) has shed light not only on the pathways by which dietary sterols may traffic but also on how the mammalian body rids itself of cholesterol and defends against xenosterols. Two genes, ABCG5 and ABCG8, located at the sitosterolemia locus, each encodes a membrane-bound ABC half-transporter and constitutes a functional unit whose activity has now been shown to account for biliary and intestinal sterol excretion. Knockout mice deficient in Abcg5 or Abcg8 recapitulate many of the phenotypic features of sitosterolemia. During the course of our studies to characterize these knockout mice, we noted that these mice, raised on normal rodent chow, exhibited infertility as well as loss of abdominal fat. We show that, although sitosterolemia does not lead to any structural defects or to any overt endocrine defects, fertility could be restored if xenosterols are specifically blocked from entry and that the loss of fat is also reversed by a variety of maneuvers that limit xenosterol accumulation. These studies show that xenosterols may have a significant biological impact on normal mammalian physiology and that the Abcg5 or Abcg8 knockout mouse model may prove useful in investigating the role of xenosterols on mammalian physiology. |
topic |
Abcg8 Abcg5 phytosterols adipocytes infertility ezetimibe |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520428056 |
work_keys_str_mv |
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