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Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis

Publication ,  Journal Article
Young, CN; Morgan, DA; Butler, SD; Rahmouni, K; Gurley, SB; Coffman, TM; Mark, AL; Davisson, RL
Published in: Molecular Metabolism
April 1, 2015

Objective: Elevations in brain angiotensin-II cause increased energy expenditure and a lean phenotype. Interestingly, the metabolic effects of increased brain angiotensin-II mimic the actions of leptin, suggesting an interaction between the two systems. Here we demonstrate that angiotensin-type 1a receptors (AT1aR) in the subfornical organ (SFO), a forebrain structure emerging as an integrative metabolic center, play a key role in the body weight-reducing effects of leptin via brown adipose tissue (BAT) thermogenesis. Methods: Cre/LoxP technology coupled with targeted viral delivery to the SFO in a mouse line bearing a conditional allele of the Agtr1a gene was utilized to determine the interaction between leptin and SFO AT1aR in metabolic regulation. Results: Selective deletion of AT1aR in the SFO attenuated leptin-induced weight loss independent of changes in food intake or locomotor activity. This was associated with diminished leptin-induced increases in core body temperature, blunted upregulation of BAT thermogenic markers, and abolishment of leptin-mediated sympathetic activation to BAT. Conclusions: These data identify a novel interaction between angiotensin-II and leptin in the control of BAT thermogenesis and body weight, and highlight a previously unrecognized role for the forebrain SFO in metabolic regulation.

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Published In

Molecular Metabolism

DOI

EISSN

2212-8778

Publication Date

April 1, 2015

Volume

4

Issue

4

Start / End Page

337 / 343

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

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Chicago
ICMJE
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Young, C. N., Morgan, D. A., Butler, S. D., Rahmouni, K., Gurley, S. B., Coffman, T. M., … Davisson, R. L. (2015). Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis. Molecular Metabolism, 4(4), 337–343. https://doi.org/10.1016/j.molmet.2015.01.007
Young, C. N., D. A. Morgan, S. D. Butler, K. Rahmouni, S. B. Gurley, T. M. Coffman, A. L. Mark, and R. L. Davisson. “Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis.” Molecular Metabolism 4, no. 4 (April 1, 2015): 337–43. https://doi.org/10.1016/j.molmet.2015.01.007.
Young CN, Morgan DA, Butler SD, Rahmouni K, Gurley SB, Coffman TM, et al. Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis. Molecular Metabolism. 2015 Apr 1;4(4):337–43.
Young, C. N., et al. “Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis.” Molecular Metabolism, vol. 4, no. 4, Apr. 2015, pp. 337–43. Scopus, doi:10.1016/j.molmet.2015.01.007.
Young CN, Morgan DA, Butler SD, Rahmouni K, Gurley SB, Coffman TM, Mark AL, Davisson RL. Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis. Molecular Metabolism. 2015 Apr 1;4(4):337–343.
Journal cover image

Published In

Molecular Metabolism

DOI

EISSN

2212-8778

Publication Date

April 1, 2015

Volume

4

Issue

4

Start / End Page

337 / 343

Related Subject Headings

  • 3101 Biochemistry and cell biology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology