Publication

FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]

van Zutphen, T., Stroeve, J. H. M., Yang, J., Bloks, V. W., Jurdzinski, A., Roelofsen, H., Huijkman, N. C. A., van Dijk, T. H., Vonk, R. J., van Deursen, J., Staels, B., Groen, A. K. & Kuipers, F., Sep-2019, In : Journal of Lipid Research. 60, 9, p. 1547-1561 15 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

van Zutphen, T., Stroeve, J. H. M., Yang, J., Bloks, V. W., Jurdzinski, A., Roelofsen, H., Huijkman, N. C. A., van Dijk, T. H., Vonk, R. J., van Deursen, J., Staels, B., Groen, A. K., & Kuipers, F. (2019). FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]. Journal of Lipid Research, 60(9), 1547-1561. https://doi.org/10.1194/jlr.M094508

Author

van Zutphen, Tim ; Stroeve, Johanna H M ; Yang, Jiufang ; Bloks, Vincent W ; Jurdzinski, Angelika ; Roelofsen, Han ; Huijkman, Nicolette C A ; van Dijk, Theo H ; Vonk, Roel J ; van Deursen, Jan ; Staels, Bart ; Groen, Albert K ; Kuipers, Folkert. / FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]. In: Journal of Lipid Research. 2019 ; Vol. 60, No. 9. pp. 1547-1561.

Harvard

van Zutphen, T, Stroeve, JHM, Yang, J, Bloks, VW, Jurdzinski, A, Roelofsen, H, Huijkman, NCA, van Dijk, TH, Vonk, RJ, van Deursen, J, Staels, B, Groen, AK & Kuipers, F 2019, 'FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]', Journal of Lipid Research, vol. 60, no. 9, pp. 1547-1561. https://doi.org/10.1194/jlr.M094508

Standard

FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]. / van Zutphen, Tim; Stroeve, Johanna H M; Yang, Jiufang; Bloks, Vincent W; Jurdzinski, Angelika; Roelofsen, Han; Huijkman, Nicolette C A; van Dijk, Theo H; Vonk, Roel J; van Deursen, Jan; Staels, Bart; Groen, Albert K; Kuipers, Folkert.

In: Journal of Lipid Research, Vol. 60, No. 9, 09.2019, p. 1547-1561.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

van Zutphen T, Stroeve JHM, Yang J, Bloks VW, Jurdzinski A, Roelofsen H et al. FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]. Journal of Lipid Research. 2019 Sep;60(9):1547-1561. https://doi.org/10.1194/jlr.M094508


BibTeX

@article{a721344a9e0a4c9a8a3f7786c35420c6,
title = "FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]",
abstract = "The bile acid-activated nuclear receptor, FXR (NR1H4), has been implicated in the control of lipid and energy metabolism, but its role in fat tissue, where it is moderately expressed, is not understood. In view of the recent development of FXR-targeting therapeutics for treatment of human metabolic diseases, understanding the tissue-specific actions of FXR is essential. Transgenic mice expressing human FXR in adipose tissue (aP2-hFXR mice) at three to five times higher levels than endogenous Fxr, i.e., much lower than its expression in liver and intestine, have markedly enlarged adipocytes and show extensive extracellular matrix remodeling. Ageing and exposure to obesogenic conditions revealed a strongly limited capacity for adipose expansion and development of fibrosis in adipose tissues of aP2-hFXR transgenic mice. This was associated with impaired lipid storage capacity, leading to elevated plasma free fatty acids and ectopic fat deposition in liver and muscle as well as whole-body insulin resistance. These studies establish that adipose FXR is a determinant of adipose tissue architecture and contributes to whole-body lipid homeostasis.",
keywords = "farnesoid X receptor, hypertrophy, hyperplasia, extracellular matrix, insulin resistance, FARNESOID-X-RECEPTOR, BILE-ACIDS, NUCLEAR RECEPTOR, INSULIN-RESISTANCE, ADIPOCYTE DIFFERENTIATION, GLUCOSE-METABOLISM, FAT MALABSORPTION, OBETICHOLIC ACID, DEFICIENT MICE, LIVER",
author = "{van Zutphen}, Tim and Stroeve, {Johanna H M} and Jiufang Yang and Bloks, {Vincent W} and Angelika Jurdzinski and Han Roelofsen and Huijkman, {Nicolette C A} and {van Dijk}, {Theo H} and Vonk, {Roel J} and {van Deursen}, Jan and Bart Staels and Groen, {Albert K} and Folkert Kuipers",
note = "Published under license by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2019",
month = sep,
doi = "10.1194/jlr.M094508",
language = "English",
volume = "60",
pages = "1547--1561",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC",
number = "9",

}

RIS

TY - JOUR

T1 - FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements[S]

AU - van Zutphen, Tim

AU - Stroeve, Johanna H M

AU - Yang, Jiufang

AU - Bloks, Vincent W

AU - Jurdzinski, Angelika

AU - Roelofsen, Han

AU - Huijkman, Nicolette C A

AU - van Dijk, Theo H

AU - Vonk, Roel J

AU - van Deursen, Jan

AU - Staels, Bart

AU - Groen, Albert K

AU - Kuipers, Folkert

N1 - Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2019/9

Y1 - 2019/9

N2 - The bile acid-activated nuclear receptor, FXR (NR1H4), has been implicated in the control of lipid and energy metabolism, but its role in fat tissue, where it is moderately expressed, is not understood. In view of the recent development of FXR-targeting therapeutics for treatment of human metabolic diseases, understanding the tissue-specific actions of FXR is essential. Transgenic mice expressing human FXR in adipose tissue (aP2-hFXR mice) at three to five times higher levels than endogenous Fxr, i.e., much lower than its expression in liver and intestine, have markedly enlarged adipocytes and show extensive extracellular matrix remodeling. Ageing and exposure to obesogenic conditions revealed a strongly limited capacity for adipose expansion and development of fibrosis in adipose tissues of aP2-hFXR transgenic mice. This was associated with impaired lipid storage capacity, leading to elevated plasma free fatty acids and ectopic fat deposition in liver and muscle as well as whole-body insulin resistance. These studies establish that adipose FXR is a determinant of adipose tissue architecture and contributes to whole-body lipid homeostasis.

AB - The bile acid-activated nuclear receptor, FXR (NR1H4), has been implicated in the control of lipid and energy metabolism, but its role in fat tissue, where it is moderately expressed, is not understood. In view of the recent development of FXR-targeting therapeutics for treatment of human metabolic diseases, understanding the tissue-specific actions of FXR is essential. Transgenic mice expressing human FXR in adipose tissue (aP2-hFXR mice) at three to five times higher levels than endogenous Fxr, i.e., much lower than its expression in liver and intestine, have markedly enlarged adipocytes and show extensive extracellular matrix remodeling. Ageing and exposure to obesogenic conditions revealed a strongly limited capacity for adipose expansion and development of fibrosis in adipose tissues of aP2-hFXR transgenic mice. This was associated with impaired lipid storage capacity, leading to elevated plasma free fatty acids and ectopic fat deposition in liver and muscle as well as whole-body insulin resistance. These studies establish that adipose FXR is a determinant of adipose tissue architecture and contributes to whole-body lipid homeostasis.

KW - farnesoid X receptor

KW - hypertrophy

KW - hyperplasia

KW - extracellular matrix

KW - insulin resistance

KW - FARNESOID-X-RECEPTOR

KW - BILE-ACIDS

KW - NUCLEAR RECEPTOR

KW - INSULIN-RESISTANCE

KW - ADIPOCYTE DIFFERENTIATION

KW - GLUCOSE-METABOLISM

KW - FAT MALABSORPTION

KW - OBETICHOLIC ACID

KW - DEFICIENT MICE

KW - LIVER

U2 - 10.1194/jlr.M094508

DO - 10.1194/jlr.M094508

M3 - Article

C2 - 31253637

VL - 60

SP - 1547

EP - 1561

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 9

ER -

ID: 86706539