Angiotensin AT1R expressing cells within the ventral hypothalamus modulate integrative control of cardiometabolic functions. iScience 2025 Jul 18;28(7):112797
Date
07/01/2025Pubmed ID
40585361Pubmed Central ID
PMC12205624DOI
10.1016/j.isci.2025.112797Scopus ID
2-s2.0-105007661529 (requires institutional sign-in at Scopus site)Abstract
Subtypes of agouti-related peptide (AgRP) neurons can be distinguished based upon expression of angiotensin II receptors. The type 1 subtype, which expresses the angiotensin type 1 receptor (Agtr1a), was examined for its role in the integrative control of cardiometabolic functions. Mice expressing Cre-recombinase via the Agtr1a locus received bilateral microinjection of an AAV vector encoding Cre-dependent expression of caspase-3 into the arcuate nucleus of mice housed at 22°C or 30°C. Ablation of Agtr1a + cells caused increased food intake, adiposity, resting metabolic rate and shifts in nutrient partitioning, elevated temperature preference, loss of core temperature defense, and changes in blood pressure and heart rate. Many phenotypes were ameliorated by housing animals at thermoneutrality. Thus, Agtr1a + cells in the ventral hypothalamus (including the type 1 AgRP neuron) influence cardiometabolic control through modulation of thermoregulatory responses to cold. Some functions of these cells appear to oppose canonical roles of other AgRP neuron subtypes.
Author List
Pasos J, Wagner VA, Lawton SBR, Madison AM, Nandani K, Mathieu NM, Grobe CC, Reho JJ, Freudinger BP, Sherman AJ, Brozoski DT, Morselli LL, Burnett CML, Segar JL, Nakagawa P, Sigmund CD, Grobe JLAuthors
Justin L. Grobe PhD Professor in the Physiology department at Medical College of WisconsinJohn J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
