Journal article
Role of PI3 kinase in mediating renal sympathoactivation to leptin in obesity
The FASEB journal, Vol.21(6), pp.A1193-A1193
2007
DOI: 10.1096/fasebj.21.6.A1193-b
Abstract
Leptin acts in the central nervous system to decrease appetite and body weight and increase sympathetic nerve activity (SNA). Diet‐induced obesity in mice is associated with resistance to the metabolic actions of leptin but preservation of its renal SNA and arterial pressure effects, leading to hypertension. The molecular basis of this selectivity in leptin resistance remains unknown. We have previously shown that leptin activation of renal SNA is phosphoinositol‐3 kinase (PI3K)‐dependent. Here, we tested the hypothesis that in obesity, renal sympathoactivation to leptin is mediated by PI3K. We compared the effect of intracerebroventricular (ICV) leptin on renal SNA in presence or absence of PI3K inhibitor, LY294002. Multifiber recording of SNA was performed under anesthesia (α‐chloralose). Obesity was induced in C57BL/6J mice by exposure to a high fat diet (45%) for 20 weeks. After 20 weeks, mice on high‐fat diet weighed ~20% more than those fed the normal diet. Weight of fat pads and plasma leptin were also significantly higher in the obese mice. The rise in renal SNA induced by ICV administration of leptin (5 μg) was of the same magnitude in both lean and obese mice. As expected, in lean mice ICV pre‐treatment with LY294001 (0.1 μg) inhibited the increase in renal SNA induced by ICV leptin (Figure). Pre‐treatment with LY294002 also blocked the increase in renal SNA induced by leptin in the obese mice (Figure). Our data confirm the pivotal role of PI3K in mediating the effects of leptin on renal SNA. Our findings also demonstrate the importance of PI3K as a key link between leptin receptor and renal SNA responses in obesity and provide a molecular substrate for selectivity in leptin resistance.
Effect of ICV leptin (5 μg) on renal SNA in lean and obese mice in presence or absence of PI3K inhibitor, LY294002 (0.1 μg). ∗ P<0.05 vs. vehicle‐leptin group, n=7–8 mice/group.
Details
- Title: Subtitle
- Role of PI3 kinase in mediating renal sympathoactivation to leptin in obesity
- Creators
- Kamal Rahmouni - University of IowaMarcelo L Correia - University of IowaDonald A Morgan - University of IowaWilliam G Haynes - University of IowaAllyn L Mark - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.21(6), pp.A1193-A1193
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A1193-b
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 2007
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine; Endocrinology and Metabolism
- Record Identifier
- 9984072095002771
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