title: Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro.
abstract: Recent evidence indicates that both leptin and eicosapentaenoic acids (EPA) improve insulin sensitivity. In the present study, we examined the effect of EPA on endogenous leptin expression in 3T3-L1 adipocytes to clarify whether the EPA's effect is exerted through leptin expression. EPA caused a time- and dose-dependent increase of leptin mRNA levels in 3T3-L1 adipocytes. Leptin mRNA expression was significantly increased up to 309.4 +/- 17.0% of the control by 24 h (P < 0.01; n = 6). Leptin secretion was also significantly increased up to 193.3 +/- 12.1% of the control by 24 h (P < 0.01; n = 6). EPA is a ligand for peroxisome proliferator-activated receptors (PPARs) with the highest affinity to PPARalpha. We examined the effect on leptin expression of clofibrate, a ligand for PPARalpha, bezafibrate, for PPARbeta, or troglitazone, for PPARgamma, to clarify whether these ligands for PPARs could mimic EPA-induced stimulation of leptin expression. Neither clofibrate nor bezafibrate affected leptin mRNA expression, whereas troglitazone significantly suppressed leptin mRNA expression. On the other hand, inhibition by 6-diazo-5-oxo-l-norleucine of the rate-limiting enzyme in hexosamine biosynthesis blunted EPA-induced stimulation of leptin mRNA expression and its secretion. These data suggest that EPA up-regulates leptin gene expression and its secretion probably through a hexosamine biosynthetic pathway.
authors.affiliation: Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: H
authors.initials: H
authors.lastname: Kaji
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Iida
authors.forename: I
authors.initials: I
authors.lastname: Mizuno
authors.forename: Y
authors.initials: Y
authors.lastname: Okimura
authors.forename: H
authors.initials: H
authors.lastname: Abe
authors.forename: K
authors.initials: K
authors.lastname: Chihara
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003980:Diazooxonorleucine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D017931:DNA Primers; D020738:Leptin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003980:Diazooxonorleucine