Angiotensin AT1R expressing cells within the ventral hypothalamus modulate integrative control of cardiometabolic functions
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 (<i>Agtr1a</i>), was examined for its role in the integrative control of cardiometabolic functions. Mice expressing Cre-recombinase via the <i>Agtr1a</i> 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 <i>Agtr1a</i> <sup>+</sup> 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, <i>Agtr1a</i> <sup>+</sup> 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.
Authors
- John J. Reho (ORCID: https://orcid.org/0000-0003-0981-3027)
- Daniel Brozoski (ORCID: https://orcid.org/0009-0006-1724-9437)
- Connie C. Grobe
- Annelise A. Madison (ORCID: https://orcid.org/0000-0001-6091-6844)
- Curt D. Sigmund (ORCID: https://orcid.org/0000-0002-1453-0921)
- Lisa Linda Morselli (ORCID: https://orcid.org/0000-0003-0514-329X)
- Colin Burnett (ORCID: https://orcid.org/0000-0001-9412-8707)
- Natalia Marin Mathieu (ORCID: https://orcid.org/0000-0003-4414-8798)
- Valerie A. Wagner (ORCID: https://orcid.org/0000-0002-4782-2664)
- Alexander J. Sherman
- Bonnie P. Freudinger
- Pablo Nakagawa (ORCID: https://orcid.org/0000-0002-1887-7367)
- Jeffrey L. Segar (ORCID: https://orcid.org/0000-0001-7311-8948)
- Justin L. Grobe (ORCID: https://orcid.org/0000-0001-9737-0873)
- Samuel Lawton
- Kush Nandani
Institutions
- Medical College of Wisconsin (US)
Publication Details
- Journal
- iScience
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1016/j.isci.2025.112797
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- 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