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All‐trans retinoic acid displays multiple effects on the growth, lipogenesis and adipokine gene expression of AML‐I preadipocyte cell line
Author(s) -
Morikawa Keiko,
Hanada Haruka,
Hirota Kaori,
aka Mitsuko,
Ikeda Chiharu
Publication year - 2013
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10005
Subject(s) - adipokine , retinoic acid , endocrinology , medicine , lipogenesis , fatty acid synthase , 3t3 l1 , retinoic acid receptor , adipose tissue , cell growth , chemistry , biology , peroxisome proliferator activated receptor , adipogenesis , cancer research , leptin , cell culture , lipid metabolism , receptor , biochemistry , genetics , obesity
Abstract 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 µM, which was accompanied by apoptosis. Western blotting showed a loss of NF‐κB, 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‐γ (PPAR‐γ) 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.