Role of intracellular calcium in human adipocyte differentiation.
Intracellular calcium ([Ca(2+)](i)) modulates adipocyte lipid metabolism and inhibits the early stages of murine adipogenesis. Consequently, we evaluated effects of increasing [Ca(2+)](i) in early and late stages of human adipocyte differentiation. Increasing [Ca(2+)](i) with either thapsigargin or A23187 at 0-1 h of differentiation markedly suppressed differentiation, with a 40-70% decrease in triglyceride accumulation and glycerol-3 phosphate dehydrogenase (GPDH) activity (P < 0.005). However, a 1-h pulse of either agent at 47-48 h only modestly inhibited differentiation. Sustained, mild stimulation of Ca(2+) influx with either agouti protein or 10 mM KCl-induced depolarization during 0-48 h of differentiation inhibited triglyceride accumulation and GPDH activity by 20-70% (P < 0.05) and markedly suppressed peroxisome proliferator-activated receptor gamma (PPARgamma) expression. These effects were reversed by Ca(2+) channel antagonism. In contrast, Ca(2+) pulses late in differentiation (71-72 h or 48-72 h) markedly increased these markers of differentiation. Thus increasing [Ca(2+)](i) appears to exert a biphasic regulatory role in human adipocyte differentiation, inhibiting the early stages while promoting the late stage of differentiation and lipid filling.
Shi
H
H
Department of Nutrition, The University of Tennessee, Knoxville, Tennessee 37996, USA.
Halvorsen
Y D
YD
Ellis
P N
PN
Wilkison
W O
WO
Zemel
M B
MB
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D054366:Agouti Signaling Protein; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007476:Ionophores / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
C515182:ASIP protein, human; D054366:Agouti Signaling Protein; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D036341:Intercellular Signaling Peptides and Proteins; D007476:Ionophores; D011506:Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D000001:Calcimycin; D011189:Potassium Chloride; D019284:Thapsigargin; D009568:Nitrendipine; D005993:Glycerolphosphate Dehydrogenase; D002118:Calcium