Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor BOC

Hye Jin Lee; Shin Bum Jo; Anthony I. Romer; Hyo Jeong Lim; Min Jung Kim; Seung Hoi Koo; Robert S. Krauss; Jong Sun Kang

doi:10.2337/db14-1017

Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor BOC

Hye Jin Lee, Shin Bum Jo, Anthony I. Romer, Hyo Jeong Lim, Min Jung Kim, Seung Hoi Koo, Robert S. Krauss, Jong Sun Kang

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Abstract

Obesity arises from a combination of genetic, environmental, and behavioral factors. However, the processes that regulate white adipose tissue (WAT) expansion at the level of the adipocyte are not well understood. The Hedgehog (HH) pathway plays a conserved role in adipogenesis, inhibiting fat formation in vivo and in vitro, but it has not been shown that mice with reduced HH pathway activity have enhanced adiposity. We report that mice lacking the HH coreceptor BOC displayed age-related overweight and excess WAT. They also displayed alterations in some metabolic parameters but normal food intake. Furthermore, they had an exacerbated response to a high-fat diet, including enhanced weight gain and adipocyte hypertrophy, livers with greater fat accumulation, and elevated expression of genes related to adipogenesis, lipid metabolism, and adipokine production. Cultured Boc^-/- mouse embryo fibroblasts showed enhanced adipogenesis relative to Boc^+/+ cells, and they expressed reduced levels of HH pathway target genes. Therefore, a loss-of-function mutation in an HH pathway component is associated with WAT accumulation and overweight in mice. Variant alleles of such HH regulators may contribute to WAT accumulation in human individuals with additional genetic or lifestyle-based predisposition to obesity.

Original language	English
Pages (from-to)	2092-2103
Number of pages	12
Journal	Diabetes
Volume	64
Issue number	6
DOIs	https://doi.org/10.2337/db14-1017
Publication status	Published - 2015 Jun

Bibliographical note

Funding Information:
This research was supported by National Institutes of Health grant AR-46207 (R.S.K.) and a National Research Foundation of Korea grant funded by the Korea Government (NRF-2011-0017315) (J.-S.K.).

Funding Information:
Funding. This research was supported by National Institutes of Health grant AR-46207 (R.S.K.) and a National Research Foundation of Korea grant funded by the Korea Government (NRF-2011-0017315) (J.-S.K.). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. H.-J.L., S.-B.J., A.I.R., H.-J.L., M.-J.K., and S.-H.K. contributed to the experimental design, research, data analysis, and review of the manuscript. R.S.K. and J.-S.K. contributed to experimental design, data analysis, and writing of the manuscript. R.S.K. and J.-S.K. are the guarantors of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. This work was presented as a poster at the International Conference of the Korean Society for Molecular and Cellular Biology, Seoul, Korea, 9–11 October 2013.

Publisher Copyright:
© 2015 by the American Diabetes Association.

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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@article{0ab0cd09828c442988d35fedaf7ea143,

title = "Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor BOC",

abstract = "Obesity arises from a combination of genetic, environmental, and behavioral factors. However, the processes that regulate white adipose tissue (WAT) expansion at the level of the adipocyte are not well understood. The Hedgehog (HH) pathway plays a conserved role in adipogenesis, inhibiting fat formation in vivo and in vitro, but it has not been shown that mice with reduced HH pathway activity have enhanced adiposity. We report that mice lacking the HH coreceptor BOC displayed age-related overweight and excess WAT. They also displayed alterations in some metabolic parameters but normal food intake. Furthermore, they had an exacerbated response to a high-fat diet, including enhanced weight gain and adipocyte hypertrophy, livers with greater fat accumulation, and elevated expression of genes related to adipogenesis, lipid metabolism, and adipokine production. Cultured Boc-/- mouse embryo fibroblasts showed enhanced adipogenesis relative to Boc+/+ cells, and they expressed reduced levels of HH pathway target genes. Therefore, a loss-of-function mutation in an HH pathway component is associated with WAT accumulation and overweight in mice. Variant alleles of such HH regulators may contribute to WAT accumulation in human individuals with additional genetic or lifestyle-based predisposition to obesity.",

author = "Lee, {Hye Jin} and Jo, {Shin Bum} and Romer, {Anthony I.} and Lim, {Hyo Jeong} and Kim, {Min Jung} and Koo, {Seung Hoi} and Krauss, {Robert S.} and Kang, {Jong Sun}",

note = "Funding Information: This research was supported by National Institutes of Health grant AR-46207 (R.S.K.) and a National Research Foundation of Korea grant funded by the Korea Government (NRF-2011-0017315) (J.-S.K.). Funding Information: Funding. This research was supported by National Institutes of Health grant AR-46207 (R.S.K.) and a National Research Foundation of Korea grant funded by the Korea Government (NRF-2011-0017315) (J.-S.K.). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. H.-J.L., S.-B.J., A.I.R., H.-J.L., M.-J.K., and S.-H.K. contributed to the experimental design, research, data analysis, and review of the manuscript. R.S.K. and J.-S.K. contributed to experimental design, data analysis, and writing of the manuscript. R.S.K. and J.-S.K. are the guarantors of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. This work was presented as a poster at the International Conference of the Korean Society for Molecular and Cellular Biology, Seoul, Korea, 9–11 October 2013. Publisher Copyright: {\textcopyright} 2015 by the American Diabetes Association.",

year = "2015",

month = jun,

doi = "10.2337/db14-1017",

language = "English",

volume = "64",

pages = "2092--2103",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

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T1 - Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor BOC

AU - Lee, Hye Jin

AU - Jo, Shin Bum

AU - Romer, Anthony I.

AU - Lim, Hyo Jeong

AU - Kim, Min Jung

AU - Koo, Seung Hoi

AU - Krauss, Robert S.

AU - Kang, Jong Sun

N1 - Funding Information: This research was supported by National Institutes of Health grant AR-46207 (R.S.K.) and a National Research Foundation of Korea grant funded by the Korea Government (NRF-2011-0017315) (J.-S.K.). Funding Information: Funding. This research was supported by National Institutes of Health grant AR-46207 (R.S.K.) and a National Research Foundation of Korea grant funded by the Korea Government (NRF-2011-0017315) (J.-S.K.). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. H.-J.L., S.-B.J., A.I.R., H.-J.L., M.-J.K., and S.-H.K. contributed to the experimental design, research, data analysis, and review of the manuscript. R.S.K. and J.-S.K. contributed to experimental design, data analysis, and writing of the manuscript. R.S.K. and J.-S.K. are the guarantors of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. This work was presented as a poster at the International Conference of the Korean Society for Molecular and Cellular Biology, Seoul, Korea, 9–11 October 2013. Publisher Copyright: © 2015 by the American Diabetes Association.

PY - 2015/6

Y1 - 2015/6

N2 - Obesity arises from a combination of genetic, environmental, and behavioral factors. However, the processes that regulate white adipose tissue (WAT) expansion at the level of the adipocyte are not well understood. The Hedgehog (HH) pathway plays a conserved role in adipogenesis, inhibiting fat formation in vivo and in vitro, but it has not been shown that mice with reduced HH pathway activity have enhanced adiposity. We report that mice lacking the HH coreceptor BOC displayed age-related overweight and excess WAT. They also displayed alterations in some metabolic parameters but normal food intake. Furthermore, they had an exacerbated response to a high-fat diet, including enhanced weight gain and adipocyte hypertrophy, livers with greater fat accumulation, and elevated expression of genes related to adipogenesis, lipid metabolism, and adipokine production. Cultured Boc-/- mouse embryo fibroblasts showed enhanced adipogenesis relative to Boc+/+ cells, and they expressed reduced levels of HH pathway target genes. Therefore, a loss-of-function mutation in an HH pathway component is associated with WAT accumulation and overweight in mice. Variant alleles of such HH regulators may contribute to WAT accumulation in human individuals with additional genetic or lifestyle-based predisposition to obesity.

AB - Obesity arises from a combination of genetic, environmental, and behavioral factors. However, the processes that regulate white adipose tissue (WAT) expansion at the level of the adipocyte are not well understood. The Hedgehog (HH) pathway plays a conserved role in adipogenesis, inhibiting fat formation in vivo and in vitro, but it has not been shown that mice with reduced HH pathway activity have enhanced adiposity. We report that mice lacking the HH coreceptor BOC displayed age-related overweight and excess WAT. They also displayed alterations in some metabolic parameters but normal food intake. Furthermore, they had an exacerbated response to a high-fat diet, including enhanced weight gain and adipocyte hypertrophy, livers with greater fat accumulation, and elevated expression of genes related to adipogenesis, lipid metabolism, and adipokine production. Cultured Boc-/- mouse embryo fibroblasts showed enhanced adipogenesis relative to Boc+/+ cells, and they expressed reduced levels of HH pathway target genes. Therefore, a loss-of-function mutation in an HH pathway component is associated with WAT accumulation and overweight in mice. Variant alleles of such HH regulators may contribute to WAT accumulation in human individuals with additional genetic or lifestyle-based predisposition to obesity.

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DO - 10.2337/db14-1017

M3 - Article

C2 - 25576054

AN - SCOPUS:84964693313

SN - 0012-1797

VL - 64

SP - 2092

EP - 2103

JO - Diabetes

JF - Diabetes

IS - 6

ER -

Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor BOC

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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