Exploration of cardiometabolic and developmental significance of angiotensinogen expression by cells expressing the leptin receptor or agouti-related peptide

Sarah A Sapouckey; Lisa L Morselli; Guorui Deng; Chetan N Patil; Kirthikaa Balapattabi; Vanessa Oliveira; Kristin E Claflin; Javier Gomez; Nicole A Pearson; Matthew J Potthoff; Katherine N Gibson-Corley; Curt D Sigmund; Justin L Grobe

doi:10.1152/ajpregu.00297.2019

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Exploration of cardiometabolic and developmental significance of angiotensinogen expression by cells expressing the leptin receptor or agouti-related peptide

Journal article

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Peer reviewed

Exploration of cardiometabolic and developmental significance of angiotensinogen expression by cells expressing the leptin receptor or agouti-related peptide

Sarah A Sapouckey, Lisa L Morselli, Guorui Deng, Chetan N Patil, Kirthikaa Balapattabi, Vanessa Oliveira, Kristin E Claflin, Javier Gomez, Nicole A Pearson, Matthew J Potthoff, …

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.318(5), pp.R855-R869

05/01/2020

DOI: 10.1152/ajpregu.00297.2019

PMCID: PMC7272763

PMID: 32186897

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Abstract

Angiotensin II (ANG II) receptor (AT ) is expressed in cells of the arcuate nucleus of the hypothalamus that express the leptin receptor ( ) and agouti-related peptide ( ). expression in these cells is required to stimulate resting energy expenditure in response to leptin and high-fat diets (HFDs), but the mechanism activating AT signaling by leptin remains unclear. To probe the role of local paracrine/autocrine ANG II generation and signaling in this mechanism, we bred mice harboring a conditional allele for angiotensinogen ( , encoding AGT) with mice expressing Cre-recombinase via the or promoters to cause cell-specific deletions of ( and mice, respectively). mice were phenotypically normal, arguing against a paracrine/autocrine AGT signaling mechanism for metabolic control. In contrast, mice exhibited reduced preweaning survival, and surviving adults exhibited altered renal structure and steroid flux, paralleling previous reports of animals with whole body deficiency or disruption in albumin ( )-expressing cells (thought to cause liver-specific disruption). Surprisingly, adult mice exhibited normal circulating AGT protein and hepatic mRNA expression but reduced mRNA expression in adrenal glands. Reanalysis of RNA-sequencing data sets describing transcriptomes of normal adrenal glands suggests that and are both expressed in this tissue, and fluorescent reporter gene expression confirms Cre activity in adrenal gland of both -Cre and -Cre mice. These findings lead to the iconoclastic conclusion that extrahepatic (i.e., adrenal) expression of is critically required for normal renal development and survival.

Receptors, Leptin - genetics

Serum Albumin - genetics

Male

Arcuate Nucleus of Hypothalamus - growth & development

Kidney - metabolism

Gene Expression Regulation, Developmental

Myocardium - metabolism

Female

Agouti-Related Protein - deficiency

Adrenal Glands - growth & development

Autocrine Communication

Paracrine Communication

Signal Transduction

Arcuate Nucleus of Hypothalamus - metabolism

Kidney - growth & development

Angiotensinogen - metabolism

Agouti-Related Protein - metabolism

Mice, Knockout

Angiotensinogen - genetics

Receptors, Leptin - deficiency

Angiotensinogen - deficiency

Animals

Adrenal Glands - metabolism

Energy Metabolism

Agouti-Related Protein - genetics

Receptors, Leptin - metabolism

Serum Albumin - metabolism

Details

Title: Subtitle: Exploration of cardiometabolic and developmental significance of angiotensinogen expression by cells expressing the leptin receptor or agouti-related peptide
Creators: Sarah A Sapouckey - Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa
Lisa L Morselli - Division of Endocrinology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Guorui Deng - Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa
Chetan N Patil - Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
Kirthikaa Balapattabi - Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
Vanessa Oliveira - Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
Kristin E Claflin - Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa
Javier Gomez - Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
Nicole A Pearson - Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa
Matthew J Potthoff - Fraternal Order of Eagles' Diabetes Research Center, University of Iowa, Iowa City, Iowa
Katherine N Gibson-Corley - Department of Pathology, University of Iowa, Iowa City, Iowa
Curt D Sigmund - Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin
Justin L Grobe - Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, Wisconsin
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.318(5), pp.R855-R869
DOI: 10.1152/ajpregu.00297.2019
PMID: 32186897
PMCID: PMC7272763
NLM abbreviation: Am J Physiol Regul Integr Comp Physiol
ISSN: 0363-6119
eISSN: 1522-1490
Publisher: American Physiological Society; United States
Grant note: R01 DK106104 / NIDDK NIH HHS P01 HL084207 / NHLBI NIH HHS R01 HL134850 / NHLBI NIH HHS S10 RR025439 / NCRR NIH HHS
Language: English
Date published: 05/01/2020
Academic Unit: Molecular Physiology and Biophysics; The University of Iowa Institute for Vision Research; Pathology; Iowa Neuroscience Institute; UI Research Foundation; Neuroscience and Pharmacology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984070365202771

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