Reduction of leptin gene expression by dietary polyunsaturated fatty acids.
Supplementation with n-3 polyunsaturated fatty acids (PUFA) for 6 weeks did not alter plasma leptin concentrations in male smokers. Changes in dietary intake of saturated fatty acids (FA) correlated positively, whereas changes in the intake of PUFA correlated negatively to changes in plasma leptin levels. A 3-week n-3 PUFA-enriched diet, as compared with a 3-week lard-enriched diet, induced lower plasma leptin concentration and reduced leptin mRNA expression in rat epididymal adipose tissue. In the human trophoblast cell line (BeWo), n-3 PUFA had a dose- and time-dependent effect on leptin expression. One mM of eicosapentaenoic acid or docosahexaenoic acid (DHA) reduced leptin expression by 71% and 78%, respectively, as compared with control, after 72 h. There was no effect on expression of the signal transducing form of the leptin receptor. In BeWo cells transfected with the human leptin promoter, we found that n-3 PUFA reduced leptin promoter activity; in contrast saturated and monounsaturated FA had no effect on leptin promoter activity. The transcription factors peroxysomal proliferator activated receptor gamma and sterol regulatory element binding protein-1 mRNAs were reduced after incubation with n-3 PUFA, whereas the expression of CCAAT/enhancer binding protein alpha was unchanged. DHA-reduced leptin expression was abolished in BeWo cells grown in cholesterol-free medium. In conclusion, n-3 FA decreased leptin gene expression both in vivo and in vitro. The direct effects of PUFA on leptin promoter activity indicate a specific regulatory action of FA on leptin expression.
Reseland
J E
JE
Institute for Nutrition Research, University of Oslo, P. O. Box 1046, Blindern, N-0316 Oslo, Norway. j.e.reseland@basalmed.uio.no
Haugen
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F
Hollung
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Solvoll
K
K
Halvorsen
B
B
Brude
I R
IR
Nenseter
M S
MS
Christiansen
E N
EN
Drevon
C A
CA
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001835:Body Weight; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D004311:Double-Blind Method; D004822:Epididymis; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D020738:Leptin / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D012907:Smoking; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000975:Antioxidants; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D054411:Receptors, Leptin; C497387:SREBF1 protein, human; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors