Journal
CELL BIOLOGY INTERNATIONAL
Volume 37, Issue 1, Pages 36-46Publisher
WILEY
DOI: 10.1002/cbin.10005
Keywords
adipocyte; adipokine; all-trans retinoic acid (ATRA); apoptosis; differentiation; growth
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Funding
- Sagami Women's University, Specified Research Grant
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Adipose tissue is a potential site of retinoic acid (RA) action, but its physiological significance remains to be clarified. We have examined the effect of all-trans retinoic acid (ATRA) on growth and differentiation of preadipocytes, and on adipokine gene expression in mature adipocytes using human preadipocyte cell model, AML-I. Both ATRA and 9-cis RA induced growth arrest in AML-I preadipocyte at between 50 and 100 mu M, which was accompanied by apoptosis. Western blotting showed a loss of NF-kappa B, Bcl-2 and p-Akt, and the accumulation of Bad and Akt in cytoplasm of ATRA-treated AML-I preadipocytes. Exposure of AML-I to ATRA or 9-cis RA increased intracellular lipid accumulation in a time-dependent manner compared to vehicle-treated cells. Expression of fatty acid synthase (FAS) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) proteins was increased in ATRA-treated cells. Thus, both ATRA and 9-cis RA promoted differentiation, inhibited proliferation and induced apoptosis in AML-I preadipocytes. ATRA also modulated adipokine expression by increasing the mRNA level of adipocytokines (adiponectin, leptin and LPL), and by inhibiting PAI-1 mRNA expression in mature AML-I adipocytes. The data suggest that ATRA exerts a wide range of effects-growth arrest, apoptosis, lipogenesis and modulation of adipokine gene expression-during the maturation of preadipocytes into adipocytes.
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