Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. / Dallner, Olof S; Marinis, Jill M; Lu, Yi-Hsueh; Birsoy, Kivanc; Werner, Emory; Fayzikhodjaeva, Gulya; Dill, Brian D; Molina, Henrik; Moscati, Arden; Kutalik, Zoltán; Marques-Vidal, Pedro; Kilpeläinen, Tuomas O; Grarup, Niels; Linneberg, Allan; Zhang, Yinxin; Vaughan, Roger; Loos, Ruth J F; Lazar, Mitchell A; Friedman, Jeffrey M.

In: Nature Medicine, Vol. 25, No. 3, 2019, p. 507-530.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Dallner, OS, Marinis, JM, Lu, Y-H, Birsoy, K, Werner, E, Fayzikhodjaeva, G, Dill, BD, Molina, H, Moscati, A, Kutalik, Z, Marques-Vidal, P, Kilpeläinen, TO, Grarup, N, Linneberg, A, Zhang, Y, Vaughan, R, Loos, RJF, Lazar, MA & Friedman, JM 2019, 'Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity', Nature Medicine, vol. 25, no. 3, pp. 507-530. https://doi.org/10.1038/s41591-019-0370-1

APA

Dallner, O. S., Marinis, J. M., Lu, Y-H., Birsoy, K., Werner, E., Fayzikhodjaeva, G., Dill, B. D., Molina, H., Moscati, A., Kutalik, Z., Marques-Vidal, P., Kilpeläinen, T. O., Grarup, N., Linneberg, A., Zhang, Y., Vaughan, R., Loos, R. J. F., Lazar, M. A., & Friedman, J. M. (2019). Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. Nature Medicine, 25(3), 507-530. https://doi.org/10.1038/s41591-019-0370-1

Vancouver

Dallner OS, Marinis JM, Lu Y-H, Birsoy K, Werner E, Fayzikhodjaeva G et al. Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. Nature Medicine. 2019;25(3):507-530. https://doi.org/10.1038/s41591-019-0370-1

Author

Dallner, Olof S ; Marinis, Jill M ; Lu, Yi-Hsueh ; Birsoy, Kivanc ; Werner, Emory ; Fayzikhodjaeva, Gulya ; Dill, Brian D ; Molina, Henrik ; Moscati, Arden ; Kutalik, Zoltán ; Marques-Vidal, Pedro ; Kilpeläinen, Tuomas O ; Grarup, Niels ; Linneberg, Allan ; Zhang, Yinxin ; Vaughan, Roger ; Loos, Ruth J F ; Lazar, Mitchell A ; Friedman, Jeffrey M. / Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. In: Nature Medicine. 2019 ; Vol. 25, No. 3. pp. 507-530.

Bibtex

@article{529a72c7d466443a87755c1334838916,
title = "Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity",
abstract = "Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we report that fat-specific and quantitative leptin expression is controlled by redundant cis elements and trans factors interacting with the proximal promoter together with a long noncoding RNA (lncOb). Diet-induced obese mice lacking lncOb show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, whereas control mice do not. Consistent with this finding, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms (SNPs) in the region of human lncOb with lower plasma leptin levels and obesity. These results show that reduced leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity and provide a framework for elucidating the pathogenic mechanism in the subset of obese patients with low endogenous leptin levels.",
author = "Dallner, {Olof S} and Marinis, {Jill M} and Yi-Hsueh Lu and Kivanc Birsoy and Emory Werner and Gulya Fayzikhodjaeva and Dill, {Brian D} and Henrik Molina and Arden Moscati and Zolt{\'a}n Kutalik and Pedro Marques-Vidal and Kilpel{\"a}inen, {Tuomas O} and Niels Grarup and Allan Linneberg and Yinxin Zhang and Roger Vaughan and Loos, {Ruth J F} and Lazar, {Mitchell A} and Friedman, {Jeffrey M}",
year = "2019",
doi = "10.1038/s41591-019-0370-1",
language = "English",
volume = "25",
pages = "507--530",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "nature publishing group",
number = "3",

}

RIS

TY - JOUR

T1 - Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity

AU - Dallner, Olof S

AU - Marinis, Jill M

AU - Lu, Yi-Hsueh

AU - Birsoy, Kivanc

AU - Werner, Emory

AU - Fayzikhodjaeva, Gulya

AU - Dill, Brian D

AU - Molina, Henrik

AU - Moscati, Arden

AU - Kutalik, Zoltán

AU - Marques-Vidal, Pedro

AU - Kilpeläinen, Tuomas O

AU - Grarup, Niels

AU - Linneberg, Allan

AU - Zhang, Yinxin

AU - Vaughan, Roger

AU - Loos, Ruth J F

AU - Lazar, Mitchell A

AU - Friedman, Jeffrey M

PY - 2019

Y1 - 2019

N2 - Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we report that fat-specific and quantitative leptin expression is controlled by redundant cis elements and trans factors interacting with the proximal promoter together with a long noncoding RNA (lncOb). Diet-induced obese mice lacking lncOb show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, whereas control mice do not. Consistent with this finding, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms (SNPs) in the region of human lncOb with lower plasma leptin levels and obesity. These results show that reduced leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity and provide a framework for elucidating the pathogenic mechanism in the subset of obese patients with low endogenous leptin levels.

AB - Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we report that fat-specific and quantitative leptin expression is controlled by redundant cis elements and trans factors interacting with the proximal promoter together with a long noncoding RNA (lncOb). Diet-induced obese mice lacking lncOb show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, whereas control mice do not. Consistent with this finding, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms (SNPs) in the region of human lncOb with lower plasma leptin levels and obesity. These results show that reduced leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity and provide a framework for elucidating the pathogenic mechanism in the subset of obese patients with low endogenous leptin levels.

U2 - 10.1038/s41591-019-0370-1

DO - 10.1038/s41591-019-0370-1

M3 - Journal article

C2 - 30842678

VL - 25

SP - 507

EP - 530

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 3

ER -

ID: 214691683