Journal article
Abstract 016: Bbs1 Gene Deletion From The Leptin Receptor Neurons Causes Obesity And Hypertension In Mice
Hypertension (Dallas, Tex. 1979), Vol.64(Suppl_1 Suppl 1), pp.A016-A016
11/2014
DOI: 10.1161/hyp.64.suppl_1.016
Abstract
Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder associated with several features including obesity and hypertension. Deletion of BBS genes globally or in the nervous system recapitulated many of the BBS phenotypes including obesity and hypertension. Here, we assessed the effect of ablating the Bbs1 gene from the neurons expressing the long signaling form of the leptin receptor (LepRb). Breeding Bbs1 with LepRb mice created mice deficient in the Bbs1 gene only in LepRb-positive neurons (visualized by tdTomato expression) as indicated by loss of leptin activation of Stat3. Importantly, Bbs1/LepR mice display an obesity phenotype as indicated by the increased (P<0.05) body weight (39±2 vs. 30±1 g in controls) and fat mass measured by MRI (14±3 vs. 4±1 g in controls) associated with increased (P<0.05) food intake (3.4±0.1 vs. 2.9±0.1 g in controls) in 25 weeks old mice. However, body weight and fat pads of pair-fed LRb/Bbs1 mice remained significantly elevated compared to controls suggesting that LRb/Bbs1 mice have reduced energy expenditure. Consistent with this possibility, LRb/Bbs1 mice displayed decreased (P<0.05) O2 consumption (2.6±0.1 vs. 3.1±0.1 mL/100g/min in controls) and heat production (8.1±0.3 vs. 9.6±0.3 kcal/kg/h in controls). These results indicate that hyperphagia and decreased energy expenditure contribute to the development of obesity in Bbs1/LepR mice. Next, we assessed the effect on arterial pressure (AP) and sympathetic nerve activity (SNA) of ablating the Bbs1 gene from the LepR-containing neurons. Interestingly, deletion of the Bbs1 gene in LepR neurons recapitulates the hypertension phenotype of BBS as indicated by elevated mean AP (125±4 vs 109±3 mmHg in controls, P=0.03). Conscious renal SNA was also elevated in LRb/Bbs1 mice relative to controls (97±8 vs 62±10 spikes/sec, P<0.05). Finally, the depressor effect of ganglionic blockade (hexamethonium) was exaggerated in Bbs1/LepR mice (-57±5 vs -38±5 mmHg in control, P=0.01). These findings demonstrate that the Bbs1 gene in LepR neurons is critical for energy homeostasis and arterial pressure regulation.
Details
- Title: Subtitle
- Abstract 016: Bbs1 Gene Deletion From The Leptin Receptor Neurons Causes Obesity And Hypertension In Mice
- Creators
- Deng Guo - the Univ of Iowa, Iowa, IADonald MorganJustin GrobeDarryl NishimuraCharles SearbyVal SheffieldKamal Rahmouni
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.64(Suppl_1 Suppl 1), pp.A016-A016
- Publisher
- American Heart Association, Inc
- DOI
- 10.1161/hyp.64.suppl_1.016
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Iowa Neuroscience Institute; Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences; Neuroscience and Pharmacology; Internal Medicine; Medical Genetics and Genomics
- Record Identifier
- 9984071961502771
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