Faculty Collaboration Database

Angiotensin AT_1A receptor signal switching in Agouti-related peptide neurons mediates metabolic rate adaptation during obesity. Cell Rep 2023 Aug 29;42(8):112935

Date

08/04/2023

Pubmed ID

37540598

Pubmed Central ID

PMC10530419

DOI

10.1016/j.celrep.2023.112935

Scopus ID

2-s2.0-85169503465 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 (AT_1A) receptors in Agouti-related peptide (AgRP) neurons contribute to the integrative control of RMR, and deletion of AT_1A from AgRP neurons causes RMR adaptation. Extracellular patch-clamp recordings identify distinct cellular responses of individual AgRP neurons from lean mice to Ang-II: no response, inhibition via AT_1A and Gαi, or stimulation via Ang-II type 2 (AT₂) receptors and Gαq. Following diet-induced obesity, a subset of Ang-II/AT_1A-inhibited AgRP neurons undergo a spontaneous G-protein "signal switch," whereby AT_1A stop inhibiting the cell via Gαi and instead begin stimulating the cell via Gαq. DREADD-mediated activation of Gαi, but not Gαq, in AT_1A-expressing AgRP cells stimulates RMR in lean and obese mice. Thus, loss of AT_1A-Gαi coupling within the AT_1A-expressing AgRP neuron subtype represents a molecular mechanism contributing to RMR adaptation.

Author List

Balapattabi K, Yavuz Y, Jiang J, Deng G, Mathieu NM, Ritter ML, Opichka MA, Reho JJ, McCorvy JD, Nakagawa P, Morselli LL, Mouradian GC Jr, Atasoy D, Cui H, Hodges MR, Sigmund CD, Grobe JL

Authors

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
John McCorvy PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Lisa Morselli MD, PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Gary C. Mouradian PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
Curt 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 Protein
Angiotensin II
Animals
Mice
Neurons
Obesity
Receptor, Angiotensin, Type 1