Increase of adipose differentiation by hypolipidemic fibrate drugs in Ob 17 preadipocytes: requirement for thyroid hormones.
The action of hypolipidemic fibrate drugs (HFD) (clofibrate, bezafibrate, fenofibrate) was studied in relation to thyroid hormone (TH) action in the TH-sensitive Ob 17 preadipocyte cells which require an early presence of TH for terminal differentiation. HFD markedly amplified the adipose differentiation and the development of several lipogenic enzymes, thus accelerating their appearance after cell growth arrest. This amplifying action could be obtained whatever the time of drug addition to the cells and required the continuous presence of the drug. HFD action was strictly dependent on the presence of TH. Within the active concentration range (0.01-0.25 mM) in serum-containing medium, HFD moderately down-modulated the nuclear TH receptor level (and c-erb alpha mRNA abundance), this being additive to the known maximal but partial down-regulation provoked by TH. The results strengthen the TH obligatory role for Ob 17 cell differentiation and give arguments against a TH-like role of HFD. In this cell line, HFD mainly behave as amplifiers for the expression of lipogenic phenotypes in already committed cells.
Gharbi-Chihi
J
J
INSERM U 38, Faculté de Médecine, Marseille, France.
Teboul
M
M
Bismuth
J
J
Bonne
J
J
Torresani
J
J
D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D051379:Mice; D008820:Mice, Obese; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics; D013963:Thyroid Hormones / Q000172:deficiency / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology
D000960:Hypolipidemic Agents; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D002994:Clofibrate; D013974:Thyroxine; D011345:Fenofibrate; D001629:Bezafibrate