Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.6.1.44 (
AGT
)
770
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Exploration of cardiometabolic and developmental significance of angiotensinogen expression by cells expressing the leptin receptor or agouti-related peptide. 3218 97
