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Physiol. Genomics 3: 75-82, 2000;
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Received 7 February 2000; accepted in final form 29 May 2000.
Physiological Genomics 3:75-82 (2000)
1094-8341/00 $5.00 © 2000 American Physiological Society

Role of intracellular calcium in human adipocyte differentiation

HANG SHI1, YUAN-DI HALVORSEN2, PAMELA N. ELLIS1, WILLIAM O. WILKISON2 and MICHAEL B. ZEMEL1

1 Department of Nutrition, The University of Tennessee, Knoxville, Tennessee 37996
2 Zen-Bio, Research Triangle Park, North Carolina 27709

Shi, Hang, Yuan-Di Halvorsen, Pamela N. Ellis, William O. Wilkison, and Michael B. Zemel. Role of intracellular calcium in human adipocyte differentiation. Physiol Genomics 3: 75–82, 2000.—Intracellular calcium ([Ca2+]i) modulates adipocyte lipid metabolism and inhibits the early stages of murine adipogenesis. Consequently, we evaluated effects of increasing [Ca2+]i in early and late stages of human adipocyte differentiation. Increasing [Ca2+]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 Ca2+ 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 (PPAR{gamma}) expression. These effects were reversed by Ca2+ channel antagonism. In contrast, Ca2+ pulses late in differentiation (71–72 h or 48–72 h) markedly increased these markers of differentiation. Thus increasing [Ca2+]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.

preadipocyte differentiation; intracellular calcium; obesity




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