Involvement of volume-sensitive Cl- channels in the proliferation of human subcutaneous pre-adipocytes.
1. Obesity is a significant challenge in terms of public health and preventive medicine. Inhibition of pre-adipocyte proliferation is believed to be important in the proposed anti-obesity mechanism. The aim of the present study was to examine the interplay between Cl(-) channels and their possible involvement in the proliferation of undifferentiated human pre-adipocytes. 2. Pre-adipocytes were isolated from human abdominal subcutaneous adipose tissue. Membrane ion currents were recorded using the whole-cell patch-clamp technique. Expression of the Cl(-) channel ClC-3 gene and protein was determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. Cell proliferation was evaluated using the [(3)H]-thymidine incorporation assay. 3. Electrophysiological recordings revealed a volume-sensitive Cl(-) current (I(Cl.vol)) expressed in pre-adipocytes that was activated under hyposmotic conditions (external osmolarity decreased by 80%) and inhibited by the Cl(-) channel blocker tamoxifen. 4. Expression of the ClC-3 channel gene and protein was confirmed by RT-PCR and western blot analysis. Blocking I(Cl.vol) with tamoxifen supressed the proliferation of pre-adipocytes in a concentration-dependent manner. 5. Collectively, the results of the present study indicate that the volume-sensitive Cl(-) channel participates in regulation of the proliferation of human subcutaneous pre-adipocytes.
Hu
Hao
H
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Li
Dong-Ling
DL
Fan
Lin
L
Ren
Jun
J
Wang
Sheng-Peng
SP
Jia
Bing
B
Liu
Bing-Hang
BH
Sun
Lei
L
Yu
Xiao-Jiang
XJ
Zang
Wei-Jin
WJ
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
D018118:Chloride Channels; C115376:ClC-3 channel; D013629:Tamoxifen