Abstract
Abstract 20340: Defect of Ca 2+ -activated Cl - Channel in Intestinal Nodose Neurons Contributes to Impaired Satiety Signal in High-Fat Diet Induced Obesity
Circulation (New York, N.Y.), Vol.130(suppl_2)
11/25/2014
DOI: 10.1161/circ.130.suppl_2.20340
Abstract
High fat diet inhibits the cholecystokinin (CCK) induced satiety signal in vagal afferents, which may contribute to the associated increased food intake. We hypothesized that a defect of Ca
2+
-activated chloride channel (CaCC) in high fat (HFD) fed mice leads to the reduction of CCK responses in intestinal vagal afferent nodose neurons. By using the whole cell patch-clamp in cultured nodose ganglia neurons isolated from C57BL/6 mice, we found that CCK (10nM) induced large inward chloride (Cl
-
) currents (36.0±11pA/pF) that were eliminated with the fast Ca
2+
chelator BAPTA (1.0±0.5pA/pF, n=7), and reduced significantly by the CaCC channel inhibitor niflumic acid (100 μM, 13.6±2.0pA/pF, p<0.05, n=8). The response to CCK in DiI-labeled proximal intestinal nodose neurons from obese mice fed a 60% HFD for 10 weeks was reduced significantly (6.1±2.9pA/pF, n=7, p<0.01) relative to control lean mice (24.8±4.9pA/pF, n=7). The underlying molecular mechanism of the reduced CCK response in mice fed a HFD did not involve altered expression of CCK receptors in nodose neurons. We found that the relative mRNA (qPCR) of CCK receptor B was not significantly changed (1.01±0.13 in control vs. 1.18±0.31 in HFD nodose ganglia, n=4, p>0.05) and the mRNA of CCK receptor A was even increased from 1.06±0.37 in control to 1.54±0.41 in HFD ganglia (n=4, p<0.05). In contrast, the CaCC channel mRNA (Ano I) was decreased to 0.61±0.09 relative to 1.01±0.20 (n=4, p<0.001), and Ano II mRNA was decreased to 0.31±0.07 relative to 1.02±0.22 (n=4, p<0.001) in nodose ganglia from HFD fed vs. control lean mice. Since the maximum current induced by a saturation level of ligand reflects the level of protein expressed on the cytoplasmic membrane, we tested the CaCC current induced by a high level of intracellular Ca
2+
(20μM). We found that the maximum current was smaller in DiI labeled intestinal nodose neurons from HFD fed mice (13.7±2.9 pA/pF vs. 26.9±3.6 pA/pF in control mice, n=10, p<0.05).
Our results indicate that CCK-activated currents recorded from intestinal vagal afferent nodose neurons are reduced in mice fed a HFD, and are associated with reduced expression of a CCK-activated Ca
2+
-dependent Cl
-
channel. This mechanism may contribute significantly to HFD-induced suppression of the satiety reflex.
Details
- Title: Subtitle
- Abstract 20340: Defect of Ca 2+ -activated Cl - Channel in Intestinal Nodose Neurons Contributes to Impaired Satiety Signal in High-Fat Diet Induced Obesity
- Creators
- Runping Wang - University of IowaYongjun Lu - University of IowaMichael Z Cicha - University of IowaKamal Rahmouni - University of IowaMark W Chapleau - University of IowaChristopher J Benson - University of IowaFrançois M Abboud - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.130(suppl_2)
- DOI
- 10.1161/circ.130.suppl_2.20340
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/25/2014
- Academic Unit
- Molecular Physiology and Biophysics; Neuroscience and Pharmacology; Fraternal Order of Eagles Diabetes Research Center; Cardiovascular Medicine; Internal Medicine; Nephrology; Iowa Neuroscience Institute; Stead Family Department of Pediatrics; Critical Care
- Record Identifier
- 9984302196902771
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