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Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b

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Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. / Kornfeld, Jan-Wilhelm; Baitzel, Catherina; Könner, A Christine; Nicholls, Hayley T; Vogt, Merly C; Herrmanns, Karolin; Scheja, Ludger; Haumaitre, Cécile; Wolf, Anna M; Knippschild, Uwe; Seibler, Jost; Cereghini, Silvia; Heeren, Joerg; Stoffel, Markus; Brüning, Jens C.

In: NATURE, Vol. 494, No. 7435, 07.02.2013, p. 111-5.

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

Harvard

Kornfeld, J-W, Baitzel, C, Könner, AC, Nicholls, HT, Vogt, MC, Herrmanns, K, Scheja, L, Haumaitre, C, Wolf, AM, Knippschild, U, Seibler, J, Cereghini, S, Heeren, J, Stoffel, M & Brüning, JC 2013, 'Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b', NATURE, vol. 494, no. 7435, pp. 111-5. https://doi.org/10.1038/nature11793

APA

Kornfeld, J-W., Baitzel, C., Könner, A. C., Nicholls, H. T., Vogt, M. C., Herrmanns, K., Scheja, L., Haumaitre, C., Wolf, A. M., Knippschild, U., Seibler, J., Cereghini, S., Heeren, J., Stoffel, M., & Brüning, J. C. (2013). Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. NATURE, 494(7435), 111-5. https://doi.org/10.1038/nature11793

Vancouver

Kornfeld J-W, Baitzel C, Könner AC, Nicholls HT, Vogt MC, Herrmanns K et al. Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. NATURE. 2013 Feb 7;494(7435):111-5. https://doi.org/10.1038/nature11793

Bibtex

@article{2df42f5f8fe44c8795ba28cf7a17bde0,
title = "Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b",
abstract = "Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism. MicroRNA (miRNA)-dependent post-transcriptional gene silencing has been recognized recently to control gene expression in disease development and progression, including that of insulin-resistant type 2 diabetes. The deregulation of miRNAs miR-143 (ref. 4), miR-181 (ref. 5), and miR-103 and miR-107 (ref. 6) alters hepatic insulin sensitivity. Here we report that the expression of miR-802 is increased in the liver of two obese mouse models and obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, whereas reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b (also known as Tcf2) as a target of miR-802-dependent silencing, and show that short hairpin RNA (shRNA)-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signalling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in Lepr(db/db) mice. Thus, this study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism through targeting of Hnf1b, and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.",
keywords = "Animals, Gene Expression Regulation, Gene Silencing, Gluconeogenesis, Glucose, Glucose Intolerance, Hepatocyte Nuclear Factor 1-beta, Humans, Insulin, Insulin Resistance, Liver, Mice, MicroRNAs, Obesity, Signal Transduction",
author = "Jan-Wilhelm Kornfeld and Catherina Baitzel and K{\"o}nner, {A Christine} and Nicholls, {Hayley T} and Vogt, {Merly C} and Karolin Herrmanns and Ludger Scheja and C{\'e}cile Haumaitre and Wolf, {Anna M} and Uwe Knippschild and Jost Seibler and Silvia Cereghini and Joerg Heeren and Markus Stoffel and Br{\"u}ning, {Jens C}",
year = "2013",
month = feb,
day = "7",
doi = "10.1038/nature11793",
language = "English",
volume = "494",
pages = "111--5",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7435",

}

RIS

TY - JOUR

T1 - Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b

AU - Kornfeld, Jan-Wilhelm

AU - Baitzel, Catherina

AU - Könner, A Christine

AU - Nicholls, Hayley T

AU - Vogt, Merly C

AU - Herrmanns, Karolin

AU - Scheja, Ludger

AU - Haumaitre, Cécile

AU - Wolf, Anna M

AU - Knippschild, Uwe

AU - Seibler, Jost

AU - Cereghini, Silvia

AU - Heeren, Joerg

AU - Stoffel, Markus

AU - Brüning, Jens C

PY - 2013/2/7

Y1 - 2013/2/7

N2 - Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism. MicroRNA (miRNA)-dependent post-transcriptional gene silencing has been recognized recently to control gene expression in disease development and progression, including that of insulin-resistant type 2 diabetes. The deregulation of miRNAs miR-143 (ref. 4), miR-181 (ref. 5), and miR-103 and miR-107 (ref. 6) alters hepatic insulin sensitivity. Here we report that the expression of miR-802 is increased in the liver of two obese mouse models and obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, whereas reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b (also known as Tcf2) as a target of miR-802-dependent silencing, and show that short hairpin RNA (shRNA)-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signalling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in Lepr(db/db) mice. Thus, this study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism through targeting of Hnf1b, and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.

AB - Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism. MicroRNA (miRNA)-dependent post-transcriptional gene silencing has been recognized recently to control gene expression in disease development and progression, including that of insulin-resistant type 2 diabetes. The deregulation of miRNAs miR-143 (ref. 4), miR-181 (ref. 5), and miR-103 and miR-107 (ref. 6) alters hepatic insulin sensitivity. Here we report that the expression of miR-802 is increased in the liver of two obese mouse models and obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, whereas reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b (also known as Tcf2) as a target of miR-802-dependent silencing, and show that short hairpin RNA (shRNA)-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signalling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in Lepr(db/db) mice. Thus, this study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism through targeting of Hnf1b, and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.

KW - Animals

KW - Gene Expression Regulation

KW - Gene Silencing

KW - Gluconeogenesis

KW - Glucose

KW - Glucose Intolerance

KW - Hepatocyte Nuclear Factor 1-beta

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Liver

KW - Mice

KW - MicroRNAs

KW - Obesity

KW - Signal Transduction

U2 - 10.1038/nature11793

DO - 10.1038/nature11793

M3 - SCORING: Journal article

C2 - 23389544

VL - 494

SP - 111

EP - 115

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7435

ER -