Journal article
Ablation of the Leptin Receptor in the Hypothalamic Arcuate Nucleus Abrogates Leptin-Induced Sympathetic Activation
Circulation research, Vol.108(7), pp.808-812
04/01/2011
DOI: 10.1161/CIRCRESAHA.111.240226
PMCID: PMC3072835
PMID: 21311043
Abstract
Rationale: The hypothalamic arcuate nucleus (ARC) is considered a major site for leptin signaling that regulates several physiological processes.
Objective: To test the hypothesis that leptin receptor in the ARC is required to mediate leptin-induced sympathetic activation.
Methods and results: First, we used the ROSA Cre-reporter mice to establish the feasibility of driving Cre expression in the ARC in a controlled manner with bilateral microinjection of adenovirus-expressing Cre-recombinase (Ad-Cre). Ad-Cre microinjection into the ARC of ObR(flox/flox) mice robustly reduced ObR expression and leptin-induced Stat3 activation in the ARC but not in the adjacent nuclei, confirming the efficacy and selectivity of the ARC deletion of ObR. Critically, deletion of ObR in the ARC attenuated brown adipose tissue and renal sympathetic nerve responses to leptin. We also examined whether ObR in the ARC is required for the preserved leptin-induced increase in renal sympathetic activity in dietary obesity. We found that deletion of ARC ObR abrogated leptin-induced increases in renal sympathetic discharge and resolved arterial pressure elevation in diet-induced obese ObR(flox/flox) mice.
Conclusions: These data demonstrate a critical role for ObR in the ARC in mediating the sympathetic nerve responses to leptin and in the adverse sympathoexcitatory effects of leptin in obesity.
Details
- Title: Subtitle
- Ablation of the Leptin Receptor in the Hypothalamic Arcuate Nucleus Abrogates Leptin-Induced Sympathetic Activation
- Creators
- Shannon M Harlan - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IADonald A Morgan - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IAKhristofor Agassandian - Department of Anatomy & Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IADeng-Fu Guo - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IAMartin D Cassell - Department of Anatomy & Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IACurt D Sigmund - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IAAllyn L Mark - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IAKamal Rahmouni - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.108(7), pp.808-812
- DOI
- 10.1161/CIRCRESAHA.111.240226
- PMID
- 21311043
- PMCID
- PMC3072835
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Grant note
- P01 HL084207-04 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 04/01/2011
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040274002771
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