¹Department of Metabolic Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co. Ltd, Osaka, Japan

²Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Gainesville, Florida, USA

³Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida, USA

Correspondence to: Y Hatakeyama, Department of Metabolic Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co. Ltd, 1-6 Kashima 2-chome, Yodogawa-ku, Osaka 532-8514, Japan. E-mail: yoshifumi_hatakeyama@po.fujisawa.co.jp

OBJECTIVE: To increase the understanding of the transcriptional regulation of UCP2 gene expression in skeletal muscle cells, we examined the effect of all-trans-retinoic acid (tRA), a ligand (after the conversion to 9-cis-RA) of the retinoid X receptor (RXR), and linolenic acid, a polyunsaturated fatty acid and peroxisome proliferator-activated receptors (PPARs) ligand, on the expression of UCP2 mRNA in cultured L₆ myotubes.

RESEARCH METHODS AND PROCEDURES: UCP2 gene expression in L₆ myotubes was confirmed by Northern blot analysis. The time- and concentration-dependency of tRA and linolenic acid on UCP2 gene expression was assessed by dot blot quantification. The mRNA levels of PPAR subtypes (, and ) were determined by RT-PCR.

RESULTS: tRA induced UCP2 gene expression in a time- and concentration-dependent manner. Similar to tRA, UCP2 mRNA was markedly increased by 0.5 mM linolenic acid. In L₆ myotubes, PPAR mRNA was abundant, whereas PPAR mRNA was lower and PPAR mRNA was minimal.

CONCLUSIONS: UCP2 mRNA expression in L₆ myotubes is up-regulated by tRA and linolenic acid, possibly through a mechanism involving PPAR and RXRs.

International Journal of Obesity (2001) 25, 1619-1624

PPAR; RXR; myotubes; retinoic acid; polyunsaturated fatty acid