Role of intracellular calcium in human adipocyte differentiation

Abstract

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.

Small Interfering RNA Knockdown of Calcium-independent Phospholipases A2 β or γ Inhibits the Hormone-induced Differentiation of 3T3-L1 Preadipocytes

“…Multiple reports have demonstrated an increase in intracellular calcium concentration ([Ca 2ϩ ] i ) during the early phase of 3T3-L1 and human preadipocyte differentiation inhibits hormone-induced adipogenesis (48,49). Additionally, increases in [Ca 2ϩ ] i during the later phase of human preadipocyte differentiation induces TAG synthesis and the expression of specific adipocyte markers (40). The results from the present study indicate that iPLA 2 may provide a calcium-dependent switch in the regulation of adipocyte differentiation in response to the environmental or chemical stimuli such as adrenocorticotrophic hormone (50) and some PGs (e.g.…”

“…Collectively, these results strongly support the essential role of the iPLA 2 family of enzymes in facilitating the maturation of 3T3-L1 cells into adipocytes. Because prior studies have demonstrated the importance of eicosanoid metabolites (19,21), lysolipids (22,24), and altered adipocyte calcium ion homeostasis (20,40) in adipocyte differentiation, these results suggest that the iPLA 2 family of enzymes serves a critical role in the provision of at least some of the lipid second messengers required for the execution of adipocyte differentiation programs.…”

Calcineurin Mediates the Calcium-dependent Inhibition of Adipocyte Differentiation in 3T3-L1 Cells

“…Of particular interest to the current study are the effects of intracellular calcium on adipocyte differentiation. A number of reports have demonstrated that increases in intracellular calcium concentration ([Ca 2ϩ ] i ) during the early phase of human and 3T3-L1 preadipocyte differentiation act to potently inhibit adipogenesis (15)(16)(17). However, the effects of calcium on this process may be complex, because increases in [Ca 2ϩ ] i in human preadipocytes during the later stages of dif- 1 The abbreviations used are: Mix, methylisobutylxanthine; Dex, dexamethasone; MDI, methylisobutylxanthine, dexamethasone and insulin; C/EBP, CCAAT/enhancer-binding protein; PPAR␥, peroxisome proliferator activated receptor ␥; NFAT, nuclear factor of activated T cells; [Ca 2ϩ ] i , intracellular calcium concentration; CsA, cyclosporin A; CNmut, constitutively activated calcineurin mutant; MSCV, murine stem cell virus; IRES, internal ribosomal entry sequence; pEGFP, permuted enhanced green fluorescent protein; Ab, antibody; LTR, long terminal repeat.…”

“…However, the effects of calcium on this process may be complex, because increases in [Ca 2ϩ ] i in human preadipocytes during the later stages of dif- 1 The abbreviations used are: Mix, methylisobutylxanthine; Dex, dexamethasone; MDI, methylisobutylxanthine, dexamethasone and insulin; C/EBP, CCAAT/enhancer-binding protein; PPAR␥, peroxisome proliferator activated receptor ␥; NFAT, nuclear factor of activated T cells; [Ca 2ϩ ] i , intracellular calcium concentration; CsA, cyclosporin A; CNmut, constitutively activated calcineurin mutant; MSCV, murine stem cell virus; IRES, internal ribosomal entry sequence; pEGFP, permuted enhanced green fluorescent protein; Ab, antibody; LTR, long terminal repeat. ferentiation and in Ob1774 cells appear to enhance the expression of certain markers of mature adipocytes (17)(18)(19). In this study we investigated the molecular mechanism that underlies the inhibitory effect of early increases in [Ca 2ϩ ] i on the differentiation of 3T3-L1 preadipocytes.…”

Effect of Oral Calcium Supplementation on Lipid Profile and Atherogenic Index of Plasma

“…[35][36][37][38] Vitamin D and PTH increase calcium uptake by the adipocytes promoting lipogenesis. With oral calcium supplementation, PTH and vitamin D levels are decreased and have opposite effects on the adipocytes.…”