Journal article
Mechanisms mediating renal sympathetic activation to leptin in obesity
The American journal of physiology, Vol.295(6), pp.R1730-R1736
12/01/2008
DOI: 10.1152/ajpregu.90324.2008
PMCID: PMC2685291
PMID: 18815209
Abstract
Leptin plays a critical role in the control of energy homeostasis. The sympathetic cardiovascular actions of leptin have emerged as a potential link between obesity and hypertension. We previously demonstrated that in mice, modest obesity induced by 10 wk of a high-fat diet is associated with preservation of leptin ability to increase renal sympathetic nerve activity (SNA) despite the resistance to the metabolic effects of leptin. Here, we examined whether selective leptin resistance exists in mice with late-stage diet-induced obesity (DIO) produced by 20 wk of a high-fat diet. The decrease in food intake and body weight induced by intraperitoneal or intracerebroventricular injection of leptin was significantly attenuated in the DIO mice. Regional SNA responses to intravenous leptin were also attenuated in DIO mice. In contrast, intracerebroventricularly administered leptin caused contrasting effects on regional SNA in DIO mice. Renal SNA response to intracerebroventricular leptin was preserved, whereas lumbar and brown adipose tissue SNA responses were attenuated. Intact renal SNA response to leptin combined with the increased cerebrospinal fluid leptin levels in DIO mice represents a potential mechanism for the adverse cardiovascular consequences of obesity. Lastly, we examined the role of phosphoinositol-3 kinase (PI3K) and melanocortin receptors (MCR) in mediating the preserved renal SNA response to leptin in obesity. Presence of PI3K inhibitor (LY294002) or MC3/4R antagonist (SHU9119) significantly attenuated the renal SNA response to leptin in DIO and agouti obese mice. Our results demonstrate the importance of PI3K and melanocortin receptors in the transduction of leptin-induced renal sympathetic activation in obesity.
Details
- Title: Subtitle
- Mechanisms mediating renal sympathetic activation to leptin in obesity
- Creators
- Donald A Morgan - University of Iowa, Neuroscience and PharmacologyKamal Rahmouni - University of Iowa, Neuroscience and PharmacologyDaniel R Thedens - University of Iowa, Electrical and Computer EngineeringRobert Weiss - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- The American journal of physiology, Vol.295(6), pp.R1730-R1736
- DOI
- 10.1152/ajpregu.90324.2008
- PMID
- 18815209
- PMCID
- PMC2685291
- NLM abbreviation
- Am J Physiol
- ISSN
- 0002-9513
- eISSN
- 2163-5773
- Publisher
- American Physiological Society
- Language
- English
- Date published
- 12/01/2008
- Description audience
- Academic
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984071968802771
Metrics
13 Record Views