Journal article
SerpinA3N in leptin-sensitive neurons is required for energy and glucose homeostasis and autonomic regulation
Metabolism, clinical and experimental, Vol.173, 156387
12/2025
DOI: 10.1016/j.metabol.2025.156387
PMCID: PMC12667195
PMID: 40935321
Abstract
SerpinA3N (Serpin peptidase inhibitor clade A member 3) is a serine protease inhibitor upregulated in the hypothalamus by leptin and obesity, yet its role in physiological regulation remains poorly understood. This study aims to elucidate the role of hypothalamic SerpinA3N in regulation of energy balance, glucose homeostasis, and autonomic and cardiovascular functions.
Immunostaining revealed that SerpinA3N is primarily expressed in neurons, including those expressing the leptin receptor (LepRb). Targeted deletion of SerpinA3N in LepRb neurons reduced body weight and adiposity and improved insulin sensitivity in female mice. SerpinA3N deficiency also enhanced leptin sensitivity, evidenced by amplified leptin-induced anorexia, weight loss, and LepRb signaling in the hypothalamic arcuate nucleus. Upon exposure to an obesogenic diet, mice lacking SerpinA3N in LepRb neurons exhibited attenuated weight gain, hepatic lipid accumulation and microgliosis. Notably, SerpinA3N deletion in LepRb neurons impaired baroreflex sensitivity and elevated renal sympathetic nerve activity, with dietary obesity further exacerbating sympathetic tone.
These findings identify neuronal SerpinA3N as a key regulator of energy balance, leptin and insulin sensitivity, and autonomic function.
Details
- Title: Subtitle
- SerpinA3N in leptin-sensitive neurons is required for energy and glucose homeostasis and autonomic regulation
- Creators
- Deng Fu GuoZili Luo - University of IowaAlexis Olson - University of IowaDonald A Morgan - University of IowaElizabeth A Newell - University of IowaKamal Rahmouni - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Metabolism, clinical and experimental, Vol.173, 156387
- DOI
- 10.1016/j.metabol.2025.156387
- PMID
- 40935321
- PMCID
- PMC12667195
- NLM abbreviation
- Metabolism
- ISSN
- 0026-0495
- eISSN
- 1532-8600
- Publisher
- W B SAUNDERS CO-ELSEVIER INC; PHILADELPHIA
- Grant note
- University of Iowa Carver College of MedicineUniversity of Iowa Office of the Vice President for ResearchCarver College of Medicine
This work was supported by NIH (R01 HL162773 and R01 HL172944) , VA (I01 BX004249 and IK6 BX006040) and the University of Iowa Fraternal Order of Eagles Diabetes Research Center to KR. Data presented herein were obtained at the Genomics Division of the Iowa Institute of Human Genetics (RRID: SCR_023422) which is supported, in part, by the University of Iowa Carver College of Medicine, and at the Bioinformatics Division of the Iowa Institute of Human Genetics which issupported, in part, by the University of Iowa Carver College of Medicine. The University of Iowa Central Microscopy Research Facility used for confocal imaging is a core resource supported by the University of Iowa Office of the Vice President for Research and the Carver College of Medicine.r supported, in part, by the University of Iowa Carver College of Medicine. The University of Iowa Central Microscopy Research Facility used for confocal imaging is a core resource supported by the University of Iowa Office of the Vice President for Research and the Carver College of Medicine.
- Language
- English
- Electronic publication date
- 09/09/2025
- Date published
- 12/2025
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984961104602771
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