The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance

Justin L. Grobe; Connie L. Grobe; Terry G. Beltz; Scott G. Westphal; Donald A. Morgan; Di Xu; Willem J. De Lange; Huiping Li; Koji Sakai; Daniel R. Thedens; Lisa A. Cassis; Kamal Rahmouni; Allyn L. Mark; Alan Kim Johnson; Curt D. Sigmund

doi:10.1016/j.cmet.2010.09.011

The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance

Justin L. Grobe, Connie L. Grobe, Terry G. Beltz, Scott G. Westphal, Donald A. Morgan, Di Xu, Willem J. De Lange, Huiping Li, Koji Sakai, Daniel R. Thedens, Lisa A. Cassis, Kamal Rahmouni, Allyn L. Mark, Alan Kim Johnson, Curt D. Sigmund

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134 Scopus citations

Abstract

The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.

Original language	English
Pages (from-to)	431-442
Number of pages	12
Journal	Cell Metabolism
Volume	12
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2010.09.011
State	Published - Nov 3 2010

Bibliographical note

Funding Information:
The authors would like to thank Victoria L. English, Mark S. Blumberg, Andrew J. Gall, Sara A. Romig-Martin, Ralph F. Johnson, Judith A. Herlein, Brian D. Fink, William I. Sivitz, Ella J. Born, Deborah R. Davis, and Vickie L. Akers for assistance/input on this project. This work was supported through Institutional T32 Post-Doctoral Fellowships funded by the National Institutes of Health (NIH) (J.L.G., C.L.G.), a Post-Doctoral Fellowship in Physiological Genomics from the American Physiological Society (J.L.G.), a K99/R00 Pathway to Independence Award (J.L.G., HL098276), Pre-Doctoral (D.X., 0910035G) and Post-Doctoral (H.L., 0825813G) Fellowships from the American Heart Association, and a Post-Doctoral Fellowship from the Japan Society for the Promotion of Science (K.S.), and through research support from the NIH (HL048058, HL061446, and HL084207 to C.D.S.; HL014388, DK066086, and MH080241 to A.K.J.; and HL073085 to L.A.C.; HL084207 to K.R. and A.L.M.). We also gratefully acknowledge the generous research support of the Roy J. Carver Trust.

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2010.09.011

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Grobe, J. L., Grobe, C. L., Beltz, T. G., Westphal, S. G., Morgan, D. A., Xu, D., De Lange, W. J., Li, H., Sakai, K., Thedens, D. R., Cassis, L. A., Rahmouni, K., Mark, A. L., Johnson, A. K., & Sigmund, C. D. (2010). The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance. Cell Metabolism, 12(5), 431-442. https://doi.org/10.1016/j.cmet.2010.09.011

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title = "The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance",

abstract = "The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.",

author = "Grobe, {Justin L.} and Grobe, {Connie L.} and Beltz, {Terry G.} and Westphal, {Scott G.} and Morgan, {Donald A.} and Di Xu and {De Lange}, {Willem J.} and Huiping Li and Koji Sakai and Thedens, {Daniel R.} and Cassis, {Lisa A.} and Kamal Rahmouni and Mark, {Allyn L.} and Johnson, {Alan Kim} and Sigmund, {Curt D.}",

note = "Funding Information: The authors would like to thank Victoria L. English, Mark S. Blumberg, Andrew J. Gall, Sara A. Romig-Martin, Ralph F. Johnson, Judith A. Herlein, Brian D. Fink, William I. Sivitz, Ella J. Born, Deborah R. Davis, and Vickie L. Akers for assistance/input on this project. This work was supported through Institutional T32 Post-Doctoral Fellowships funded by the National Institutes of Health (NIH) (J.L.G., C.L.G.), a Post-Doctoral Fellowship in Physiological Genomics from the American Physiological Society (J.L.G.), a K99/R00 Pathway to Independence Award (J.L.G., HL098276), Pre-Doctoral (D.X., 0910035G) and Post-Doctoral (H.L., 0825813G) Fellowships from the American Heart Association, and a Post-Doctoral Fellowship from the Japan Society for the Promotion of Science (K.S.), and through research support from the NIH (HL048058, HL061446, and HL084207 to C.D.S.; HL014388, DK066086, and MH080241 to A.K.J.; and HL073085 to L.A.C.; HL084207 to K.R. and A.L.M.). We also gratefully acknowledge the generous research support of the Roy J. Carver Trust. ",

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Grobe, JL, Grobe, CL, Beltz, TG, Westphal, SG, Morgan, DA, Xu, D, De Lange, WJ, Li, H, Sakai, K, Thedens, DR, Cassis, LA, Rahmouni, K, Mark, AL, Johnson, AK & Sigmund, CD 2010, 'The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance', Cell Metabolism, vol. 12, no. 5, pp. 431-442. https://doi.org/10.1016/j.cmet.2010.09.011

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T1 - The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance

AU - Grobe, Justin L.

AU - Grobe, Connie L.

AU - Beltz, Terry G.

AU - Westphal, Scott G.

AU - Morgan, Donald A.

AU - Xu, Di

AU - De Lange, Willem J.

AU - Li, Huiping

AU - Sakai, Koji

AU - Thedens, Daniel R.

AU - Cassis, Lisa A.

AU - Rahmouni, Kamal

AU - Mark, Allyn L.

AU - Johnson, Alan Kim

AU - Sigmund, Curt D.

N1 - Funding Information: The authors would like to thank Victoria L. English, Mark S. Blumberg, Andrew J. Gall, Sara A. Romig-Martin, Ralph F. Johnson, Judith A. Herlein, Brian D. Fink, William I. Sivitz, Ella J. Born, Deborah R. Davis, and Vickie L. Akers for assistance/input on this project. This work was supported through Institutional T32 Post-Doctoral Fellowships funded by the National Institutes of Health (NIH) (J.L.G., C.L.G.), a Post-Doctoral Fellowship in Physiological Genomics from the American Physiological Society (J.L.G.), a K99/R00 Pathway to Independence Award (J.L.G., HL098276), Pre-Doctoral (D.X., 0910035G) and Post-Doctoral (H.L., 0825813G) Fellowships from the American Heart Association, and a Post-Doctoral Fellowship from the Japan Society for the Promotion of Science (K.S.), and through research support from the NIH (HL048058, HL061446, and HL084207 to C.D.S.; HL014388, DK066086, and MH080241 to A.K.J.; and HL073085 to L.A.C.; HL084207 to K.R. and A.L.M.). We also gratefully acknowledge the generous research support of the Roy J. Carver Trust.

PY - 2010/11/3

Y1 - 2010/11/3

N2 - The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.

AB - The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.

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JO - Cell Metabolism

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ER -

The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance

Abstract

Bibliographical note

ASJC Scopus subject areas

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