Abstract
Dissociating the Metabolic and Cardiovascular Effects of Leptin Through mTORC1 Signaling
The FASEB journal, Vol.29(S1)
04/2015
DOI: 10.1096/fasebj.29.1_supplement.652.20
Abstract
Abstract only
Leptin is an adipocyte‐derived hormone which acts in the brain to regulate energy homeostasis by suppressing appetite and increasing energy expenditure. Leptin also promotes arterial pressure elevation by increasing sympathetic nerve activity (SNA). Recent evidences indicate that the mechanistic target of rapamycin complex 1 (mTORC1) plays a key role in mediating the metabolic and sympathetic effects of leptin. To test the consequence of disrupting mTORC1 on leptin actions, we conditionally deleted Raptor, a critical subunit of mTORC1, in leptin receptor (LRb) expressing cells using genetically modified mice in which the Raptor gene is flanked by Lox‐P sites (Raptor
fl/fl
) and Cre recombinase driven by the LRb promoter (LRb
Cre
). We measured body weight weekly from 4 weeks of age and observed no differences between LRb
Cre
/Raptor
fl/fl
and control littermates (29.6±0.8g vs 31.0±0.8g at 14 weeks). Additionally, food intake and body weight were recorded daily at baseline and after treatment with vehicle or leptin (1mg/g bw, intraperitoneally, twice daily) for 4 days. We found no significant difference in the cumulative decrease in food intake (‐1.6±0.8g vs ‐1.1±1.7g) or body weight (‐5.9±0.8% vs ‐5.7±0.7%) caused by leptin between LRb
Cre
/Raptor
fl/fl
mice and WT littermates. Finally, we performed multifiber nerve recordings of renal SNA to determine the contribution of mTORC1 to the cardiovascular sympathetic action of leptin. Interestingly, intracerebroventricular injection of leptin (2 mg) increased renal SNA in control mice (106±20%), but not in LRb
Cre
xRaptor
fl/fl
mice (‐28±11%, P<0.05 vs controls). We concluded that mTORC1 is necessary for the renal SNA effect of leptin, but not critical for the metabolic actions of leptin.
Details
- Title: Subtitle
- Dissociating the Metabolic and Cardiovascular Effects of Leptin Through mTORC1 Signaling
- Creators
- Mohamed Rouabhi - University of IowaBalyssa Bell - University of IowaDonald Morgan - University of IowaKamal Rahmouni - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.29(S1)
- DOI
- 10.1096/fasebj.29.1_supplement.652.20
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Language
- English
- Date published
- 04/2015
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984695815702771
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