The role of GH in adipose tissue: Lessons from adipose-specific GH receptor gene-disrupted mice

Edward O. List; Darlene E. Berryman; Kevin Funk; Elahu S. Gosney; Adam Jara; Bruce Kelder; Xinyue Wang; Laura Kutz; Katie Troike; Nicholas Lozier; Vincent Mikula; Ellen R. Lubbers; Han Zhang; Clare Vesel; Riia K. Junnila; Stuart J. Frank; Michal M. Masternak; Andrzej Bartke; John J. Kopchick

doi:10.1210/me.2012-1330

The role of GH in adipose tissue: Lessons from adipose-specific GH receptor gene-disrupted mice

Edward O. List, Darlene E. Berryman, Kevin Funk, Elahu S. Gosney, Adam Jara, Bruce Kelder, Xinyue Wang, Laura Kutz, Katie Troike, Nicholas Lozier, Vincent Mikula, Ellen R. Lubbers, Han Zhang, Clare Vesel, Riia K. Junnila, Stuart J. Frank, Michal M. Masternak, Andrzej Bartke, John J. Kopchick

93 Citations (Scopus)

Abstract

GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR-/- mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR-/- mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/- mice. Like the GHR-/- mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/- mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism.

Original language	English
Journal	Molecular Endocrinology
Volume	27
Issue number	3
Pages (from-to)	524-535
Number of pages	12
ISSN	0888-8809
DOIs	https://doi.org/10.1210/me.2012-1330
Publication status	Published - 7 Mar 2013

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List, E. O., Berryman, D. E., Funk, K., Gosney, E. S., Jara, A., Kelder, B., Wang, X., Kutz, L., Troike, K., Lozier, N., Mikula, V., Lubbers, E. R., Zhang, H., Vesel, C., Junnila, R. K., Frank, S. J., Masternak, M. M., Bartke, A., & Kopchick, J. J. (2013). The role of GH in adipose tissue: Lessons from adipose-specific GH receptor gene-disrupted mice. Molecular Endocrinology, 27(3), 524-535. https://doi.org/10.1210/me.2012-1330

List, EO, Berryman, DE, Funk, K, Gosney, ES, Jara, A, Kelder, B, Wang, X, Kutz, L, Troike, K, Lozier, N, Mikula, V, Lubbers, ER, Zhang, H, Vesel, C, Junnila, RK, Frank, SJ, Masternak, MM, Bartke, A & Kopchick, JJ 2013, 'The role of GH in adipose tissue: Lessons from adipose-specific GH receptor gene-disrupted mice', Molecular Endocrinology, vol. 27, no. 3, pp. 524-535. https://doi.org/10.1210/me.2012-1330

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title = "The role of GH in adipose tissue: Lessons from adipose-specific GH receptor gene-disrupted mice",

abstract = "GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR-/- mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR-/- mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/- mice. Like the GHR-/- mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/- mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism.",

author = "List, {Edward O.} and Berryman, {Darlene E.} and Kevin Funk and Gosney, {Elahu S.} and Adam Jara and Bruce Kelder and Xinyue Wang and Laura Kutz and Katie Troike and Nicholas Lozier and Vincent Mikula and Lubbers, {Ellen R.} and Han Zhang and Clare Vesel and Junnila, {Riia K.} and Frank, {Stuart J.} and Masternak, {Michal M.} and Andrzej Bartke and Kopchick, {John J.}",

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doi = "10.1210/me.2012-1330",

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T2 - Lessons from adipose-specific GH receptor gene-disrupted mice

AU - List, Edward O.

AU - Berryman, Darlene E.

AU - Funk, Kevin

AU - Gosney, Elahu S.

AU - Jara, Adam

AU - Kelder, Bruce

AU - Wang, Xinyue

AU - Kutz, Laura

AU - Troike, Katie

AU - Lozier, Nicholas

AU - Mikula, Vincent

AU - Lubbers, Ellen R.

AU - Zhang, Han

AU - Vesel, Clare

AU - Junnila, Riia K.

AU - Frank, Stuart J.

AU - Masternak, Michal M.

AU - Bartke, Andrzej

AU - Kopchick, John J.

PY - 2013/3/7

Y1 - 2013/3/7

N2 - GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR-/- mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR-/- mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/- mice. Like the GHR-/- mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/- mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism.

AB - GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR-/- mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR-/- mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/- mice. Like the GHR-/- mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/- mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism.

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The role of GH in adipose tissue: Lessons from adipose-specific GH receptor gene-disrupted mice

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