Abstract
Abstract P323: TMEM16A and TMEM16B Contribute to Mice Cholecystokinin Response in Sex-Specific Manner
Hypertension (Dallas, Tex. 1979), Vol.72(Suppl_1)
09/2018
DOI: 10.1161/hyp.72.suppl_1.P323
Abstract
High fat diet (HFD) leads to obesity and the metabolic syndrome. However, the effect are less pronounced in females than in males. We suggest that a gender difference is in their response to the satiety peptide Cholecystokinin (CCK). We previously reported that the Ca
2+
-activated Cl
-
channel (CaCC) subunit
Ano2
/TMEM16B is essential for the CCK-induced current in intestinal nodose neurons in male mice, and is down regulated in obese mice fed on HFD. We hypothesize that the CCK-induced current in female mice is mediated predominantly by
Ano1
/TMEM16A, the alternative subunit of TMEM16B. We studied the CCK-induced current in nodose neurons from female C57BL/6 mice using whole cell patch-clamp. We found that 10nM of CCK induces an inward current in these neurons with a current density averaging 13.4±2.5 pA/pF (n=7), and this current is inhibited to 3.1±1.2 pA/pF (n=7, p<0.01) by TMEM16A specific inhibitor T16A
inhi-A01
. We further tested whether HFD which effectively suppressed the expression of TMEM16B in male mice, would also decrease TMEM16A in female mice. Our results show that the CCK-induced TMEM16A current in nodose neurons is not decreased in female, but tend to increase from 12.5±1.6 (n=10) in control to 17.4±4.1 pA/pF (n=11, p=0.298) in female mice fed on HFD. Concurrently the mRNA level of
Ano1
in mice fed on HFD also show a trend to increase by 1.33±0.41 fold (n=2 pairs of mice, p=0.37) compared to mice on regular chow. Our findings indicate that activation of CCK-sensitive
Ano1
/TMEM16A may partially protect female mice from HFD induced obesity and metabolic syndrome.
Details
- Title: Subtitle
- Abstract P323: TMEM16A and TMEM16B Contribute to Mice Cholecystokinin Response in Sex-Specific Manner
- Creators
- Runping Wang - University of IowaMichael Z Cicha - University of IowaMark W Chapleau - University of IowaFrancois M Abboud - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.72(Suppl_1)
- DOI
- 10.1161/hyp.72.suppl_1.P323
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2018
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Nephrology
- Record Identifier
- 9984302189102771
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