Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH

Min Woo Lee; Dipanjan Chanda; Jianqi Yang; Hyunhee Oh; Su Sung Kim; Young Sil Yoon; Sungpyo Hong; Keun Gyu Park; In Kyu Lee; Cheol Soo Choi; Richard W. Hanson; Hueng Sik Choi; Seung Hoi Koo

doi:10.1016/j.cmet.2010.02.016

Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH

Min Woo Lee, Dipanjan Chanda, Jianqi Yang, Hyunhee Oh, Su Sung Kim, Young Sil Yoon, Sungpyo Hong, Keun Gyu Park, In Kyu Lee, Cheol Soo Choi, Richard W. Hanson, Hueng Sik Choi, Seung Hoi Koo

Research output: Contribution to journal › Article › peer-review

164 Citations (Scopus)

Abstract

Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1α-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N). Overexpression of constitutively active CREBH activates transcription of PEPCK-C or G6Pase by binding to its enhancer site that is distinct from the well-characterized CREB/CRTC2 regulatory sequences in vivo. Of interest, knockdown of CREBH in liver significantly reduces blood glucose levels without altering expression of genes involved in the ER stress signaling cascades in mice. These data suggest a crucial role for CREBH in the regulation of hepatic glucose metabolism in mammals.

Original language	English
Pages (from-to)	331-339
Number of pages	9
Journal	Cell Metabolism
Volume	11
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2010.02.016
Publication status	Published - 2010 Apr 7
Externally published	Yes

Bibliographical note

Funding Information:
We would like to thank Sun Myung Park and Yo-Na Kim for technical assistance. We would also like to thank Dr. Seok-Yong Choi for critical reading. This work was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A080150) (S.-H.K.) and by the NRF through the National Research Laboratory program (NRL-ROA-2005-000-10047-0) (H.-S.C.).

Keywords

HUMDISEASE

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2010.02.016

Cite this

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title = "Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH",

abstract = "Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1α-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N). Overexpression of constitutively active CREBH activates transcription of PEPCK-C or G6Pase by binding to its enhancer site that is distinct from the well-characterized CREB/CRTC2 regulatory sequences in vivo. Of interest, knockdown of CREBH in liver significantly reduces blood glucose levels without altering expression of genes involved in the ER stress signaling cascades in mice. These data suggest a crucial role for CREBH in the regulation of hepatic glucose metabolism in mammals.",

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author = "Lee, {Min Woo} and Dipanjan Chanda and Jianqi Yang and Hyunhee Oh and Kim, {Su Sung} and Yoon, {Young Sil} and Sungpyo Hong and Park, {Keun Gyu} and Lee, {In Kyu} and Choi, {Cheol Soo} and Hanson, {Richard W.} and Choi, {Hueng Sik} and Koo, {Seung Hoi}",

note = "Funding Information: We would like to thank Sun Myung Park and Yo-Na Kim for technical assistance. We would also like to thank Dr. Seok-Yong Choi for critical reading. This work was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A080150) (S.-H.K.) and by the NRF through the National Research Laboratory program (NRL-ROA-2005-000-10047-0) (H.-S.C.). ",

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AU - Kim, Su Sung

AU - Yoon, Young Sil

AU - Hong, Sungpyo

AU - Park, Keun Gyu

AU - Lee, In Kyu

AU - Choi, Cheol Soo

AU - Hanson, Richard W.

AU - Choi, Hueng Sik

AU - Koo, Seung Hoi

N1 - Funding Information: We would like to thank Sun Myung Park and Yo-Na Kim for technical assistance. We would also like to thank Dr. Seok-Yong Choi for critical reading. This work was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A080150) (S.-H.K.) and by the NRF through the National Research Laboratory program (NRL-ROA-2005-000-10047-0) (H.-S.C.).

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N2 - Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1α-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N). Overexpression of constitutively active CREBH activates transcription of PEPCK-C or G6Pase by binding to its enhancer site that is distinct from the well-characterized CREB/CRTC2 regulatory sequences in vivo. Of interest, knockdown of CREBH in liver significantly reduces blood glucose levels without altering expression of genes involved in the ER stress signaling cascades in mice. These data suggest a crucial role for CREBH in the regulation of hepatic glucose metabolism in mammals.

AB - Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1α-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N). Overexpression of constitutively active CREBH activates transcription of PEPCK-C or G6Pase by binding to its enhancer site that is distinct from the well-characterized CREB/CRTC2 regulatory sequences in vivo. Of interest, knockdown of CREBH in liver significantly reduces blood glucose levels without altering expression of genes involved in the ER stress signaling cascades in mice. These data suggest a crucial role for CREBH in the regulation of hepatic glucose metabolism in mammals.

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Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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