Angiotensin AT1R expressing cells within the ventral hypothalamus modulate integrative control of cardiometabolic functions
Year: 2025
Type: article
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.
Source: iScience
Authors: Jhonatan Pasos, Valerie A. Wagner, Samuel B.R. Lawton, Alyssa M. Madison, Kush Nandani, Natalia M. Mathieu, Connie C. Grobe, John J. Reho, Bonnie P. Freudinger, Alexander J. Sherman, Daniel T. Brozoski, Lisa L. Morselli, Colin M.L. Burnett, Jeffrey L. Segar, Pablo Nakagawa, Curt D. Sigmund, Justin L. Grobe
Institutions: Medical College of Wisconsin, Universidad CES
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
Funders: Advancing a Healthier Wisconsin Endowment, Medical College of Wisconsin, Children’s Hospital of Wisconsin Research Institute, National Institutes of Health, Diabetes Research and Training Center, National Heart, Lung, and Blood Institute, NIH Office of the Director, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G18062229, G2265858455, G2279093208, G2383519555, G3008918083, G331478883, G352720048, G3540098788, G4359274817, G5181251264, 3D Printer, G546620678, G5896623678, G6839489586, Medical Scientist Training Program, G7367663526, Clinical and Translational Science Award, G7996544324, PPARG-dependent Mechanisms Control Endothelial-Smooth Muscle Coordination, Arterial Pressure, Vasomotor Function and Arterial Stiffness, Angiotensin receptor G protein signal switching in AgRP neurons in cardiometabolic control, Impact of Early Life Sodium Intake on Growth and Metabolism – Role of Hypothalamic Mechanisms, Intersection of the PPARγ-RhoBTB1-Cullin-3 Pathway and Renin-Angiotensin System in Blood Pressure, Vascular Function and Arterial Stiffness
OpenAlex ID: W4410877847