Journal article
Melanocortin MC4R receptor is required for energy expenditure but not blood pressure effects of angiotensin II within the mouse brain
Physiological genomics, Vol.54(6), pp.196-205
04/27/2022
DOI: 10.1152/physiolgenomics.00015.2022
PMCID: PMC9131927
PMID: 35476598
Abstract
The brain renin-angiotensin system (RAS) is implicated in control of blood pressure (BP), fluid intake, and energy expenditure (EE). Angiotensin II (ANG) within the arcuate nucleus of the hypothalamus contributes to control of resting metabolic rate (RMR) and thereby EE through its actions upon Agouti-related peptide (AgRP) neurons, which also contribute to EE control by leptin. First, we determined that although leptin stimulates EE in control littermates, mice with transgenic activation of the brain RAS (sRA) exhibit increased EE - and leptin has no additive effect to exaggerate EE in these mice. These findings led us to hypothesize that leptin and ANG in the brain stimulate EE through a shared mechanism. Because AgRP signaling to the melanocortin MC
R receptor contributes to the metabolic effects of leptin, we performed a series of studies examining RMR, fluid intake, and BP responses to ANG in mice rendered deficient for expression of MC
R via a transcriptional block (Mc4r-TB). These mice were resistant to stimulation of RMR in response to activation of the endogenous brain RAS via chronic deoxycorticosterone acetate (DOCA)-salt treatment, while fluid & electrolyte effects remained intact. These mice were also resistant to stimulation of RMR via acute ICV injection of ANG, while BP responses to ICV ANG remained intact. Collectively, these data demonstrate that the effects of ANG within the brain to control RMR and EE are dependent upon MC
R signaling, while fluid homeostasis and BP responses are independent of MC
R signaling.
Details
- Title: Subtitle
- Melanocortin MC4R receptor is required for energy expenditure but not blood pressure effects of angiotensin II within the mouse brain
- Creators
- Vanessa Oliveira - Medical College of WisconsinRuth A Riedl - Baylor College of MedicineKristin E Claflin - University of IowaNatalia Marin Mathieu - Medical College of WisconsinMcKenzie L Ritter - Medical College of WisconsinKirthikaa Balapattabi - Medical College of WisconsinKelsey K Wackman - Medical College of WisconsinJohn J Reho - Medical College of WisconsinDaniel T Brozoski - Medical College of WisconsinDonald A Morgan - University of IowaHuxing Cui - University of IowaKamal Rahmouni - University of IowaColin M L Burnett - University of IowaPablo Nakagawa - Medical College of WisconsinCurt D Sigmund - Medical College of WisconsinLisa L Morselli - Medical College of WisconsinJustin L Grobe - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Physiological genomics, Vol.54(6), pp.196-205
- DOI
- 10.1152/physiolgenomics.00015.2022
- PMID
- 35476598
- PMCID
- PMC9131927
- ISSN
- 1094-8341
- eISSN
- 1531-2267
- Grant note
- 903246 / American Heart Association (AHA) HL007485 / HHS | National Institutes of Health (NIH) HL144807 / HHS | National Institutes of Health (NIH) HL153274 / HHS | National Institutes of Health (NIH) HL127673 / HHS | National Institutes of Health (NIH) 18EIA33890055 / American Heart Association (AHA) 898067 / American Heart Association (AHA) HL134850 / HHS | National Institutes of Health (NIH) UL1TR001436 / HHS | National Institutes of Health (NIH) HL153101 / HHS | National Institutes of Health (NIH) HL084207 / HHS | National Institutes of Health (NIH)
- Language
- English
- Date published
- 04/27/2022
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984251631802771
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