Potential mechanisms of hypothalamic renin-angiotensin system activation by leptin and DOCA-salt for the control of resting metabolism. Physiol Genomics 2017 Dec 01;49(12):722-732
Date
10/08/2017Pubmed ID
28986397Pubmed Central ID
PMC5814669DOI
10.1152/physiolgenomics.00087.2017Scopus ID
2-s2.0-85044192981 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
The renin-angiotensin system (RAS), originally described as a circulating hormone system, is an enzymatic cascade in which the final vasoactive peptide angiotensin II (ANG) regulates cardiovascular, hydromineral, and metabolic functions. The RAS is also synthesized locally in a number of tissues including the brain, where it can act in a paracrine fashion to regulate blood pressure, thirst, fluid balance, and resting energy expenditure/resting metabolic rate (RMR). Recent studies demonstrate that ANG AT1A receptors (Agtr1a) specifically in agouti-related peptide (AgRP) neurons of the arcuate nucleus (ARC) coordinate autonomic and energy expenditure responses to various stimuli including deoxycorticosterone acetate (DOCA)-salt, high-fat feeding, and leptin. It remains unclear, however, how these disparate stimuli converge upon and activate this specific population of AT1A receptors in AgRP neurons. We hypothesize that these stimuli may act to stimulate local expression of the angiotensinogen (AGT) precursor for ANG, or the expression of AT1A receptors, and thereby local activity of the RAS within the (ARC). Here we review mechanisms that may control AGT and AT1A expression within the central nervous system, with a particular focus on mechanisms activated by steroids, dietary fat, and leptin.
Author List
Sapouckey SA, Deng G, Sigmund CD, Grobe JLAuthors
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinCurt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Agouti-Related ProteinAngiotensins
Animals
Arcuate Nucleus of Hypothalamus
Desoxycorticosterone Acetate
Humans
Hypothalamus
Leptin
Renin-Angiotensin System
