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• W3010831855 abstract "Angiotensin II (ANG II) Agtr1a receptor (AT 1A ) is expressed in cells of the arcuate nucleus of the hypothalamus that express the leptin receptor ( Lepr) and agouti-related peptide ( Agrp). Agtr1a 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 1A 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 ( Agt, encoding AGT) with mice expressing Cre-recombinase via the Lepr or Agrp promoters to cause cell-specific deletions of Agt ( Agt Lepr -KO and Agt Agrp -KO mice, respectively). Agt Lepr -KO mice were phenotypically normal, arguing against a paracrine/autocrine AGT signaling mechanism for metabolic control. In contrast, Agt Agrp -KO mice exhibited reduced preweaning survival, and surviving adults exhibited altered renal structure and steroid flux, paralleling previous reports of animals with whole body Agt deficiency or Agt disruption in albumin ( Alb)-expressing cells (thought to cause liver-specific disruption). Surprisingly, adult Agt Agrp -KO mice exhibited normal circulating AGT protein and hepatic Agt mRNA expression but reduced Agt mRNA expression in adrenal glands. Reanalysis of RNA-sequencing data sets describing transcriptomes of normal adrenal glands suggests that Agrp and Alb are both expressed in this tissue, and fluorescent reporter gene expression confirms Cre activity in adrenal gland of both Agrp-Cre and Alb-Cre mice. These findings lead to the iconoclastic conclusion that extrahepatic (i.e., adrenal) expression of Agt is critically required for normal renal development and survival." @default.
• W3010831855 created "2020-03-23" @default.
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• W3010831855 date "2020-05-01" @default.
• W3010831855 modified "2023-10-15" @default.
• W3010831855 title "Exploration of cardiometabolic and developmental significance of angiotensinogen expression by cells expressing the leptin receptor or agouti-related peptide" @default.
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• W3010831855 doi "https://doi.org/10.1152/ajpregu.00297.2019" @default.
• W3010831855 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7272763" @default.
• W3010831855 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32186897" @default.
• W3010831855 hasPublicationYear "2020" @default.
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