Summary
The transcription factor, sterol regulatory binding protein 1c (also called adipocyte determination and differentiation-dependent factor 1), stimulates transcription of the messenger ribonucleic acids (mRNAs) for lipid synthesis enzymes. Hepatic ADD1 transcripts are reduced by polyunsaturated fatty acids (PUFAs). The ADD1 transcripts are expressed to a considerable extent in porcine adipocytes. Consequently, it was of interest to examine the effects of several PUFAs on ADD1 in a tissue wherein several long-chain fatty acids (FAs) increase adipocyte differentiation. The effects of arachidonic acid (C20∶4), docosahexaenoic acid (C22∶6), and cis 9, trans 11-conjugated linoleic acid (9,11-CLA) on differentiating preadipocyte ADD1 mRNA and protein and on preadipocyte differentiation were determined. Porcine stromal-vascular cells were plated in serum-containing medium and differentiated in serum-free medium containing insulin, hydrocortisone, and transferrin ± an individual FA. After 24-h differentiation ± FA, plates were stained with Oil Red O as an indicator of differentiation or total RNA was extracted or a nuclear fraction was isolated for protein measurement. Addition of C20∶4 or 9,11-CLA increased the number of Oil Red O-stained cells or the Oil Red O-stained material, whereas C22∶6 did not. Addition of C20∶4, C22∶6, or 9,11-CLA decreased the concentration of the mRNA and protein for ADD1. Thus, although all three FAs decreased the ADD1 mRNA and protein concentrations, C20∶4 and 9,11-CLA increased differentiation, measured by Oil Red O staining, whereas C22∶6 did not. The data suggest that the regulation of differentiation and mRNAs by individual FAs may involve distinct mechanisms.
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References
Amri, E. Z.; Bertrand, B.; Ailhaud, G.; Grimaldi, P. Regulation of adipose cell differentiation. I. Fatty acids are inducers of the ap2 gene expression. J. Lipid Res. 32:1449–1456; 1991.
Belury, M. A.; Vanden Heuval, J. P. Modulation of diabetes by conjugated linoleic acid. In: Yurawecz, M. P.; Mossoba, M. M.; Kramer, J. K. G.; Pariza, M. W.; Nelson, G. J., ed. Advances in in conjugated linoleic acid research 1. Champaign, IL: AOCS Press; 1999:404–411.
Brodie, A. E.; Manning, V. A.; Ferguson, K. R.; Jewell, D. E.; Hu, C. Y. Conjugated linoleic acid inhibits differentiation of pre- and post-confluent 3t3-11 preadipocytes but inhibits cell proliferation only in preconfluent cells. J. Nutr. 129:602–606; 1999.
Brun, R. P.; Kim, J. B.; Hu, E.; Spiegelman, B. M. Peroxisome proliferator-activated receptor gamma and the control of adipogenesis. Curr. Opin. Lipidol. 8:212–218; 1997.
Burnette, W. N. “Western blotting”: electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein a. Anal. Biochem. 112:195–203; 1981.
Ding, S. T.; McNeel, R. L.; Mersmann, H. J. Expression of porcine adipocyte transcripts: tissue distribution and differentiation in vitro and in vivo. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 123:307–318; 1999.
Ding, S.-T.; McNeel, R. L.; Mersmann, H. J. Conjugated linoleic acid increases the differentiation of porcine adipocytes in vitro. Nutr. Res. 20:1569–1580; 2000b.
Ding, S.-T.; Mersmann, H.J. Fatty acids modulate porcine adipocyte differentiation and transcripts for transcription factors and adipocyte-characteristic proteins. J. Nutr. Biochem. 12:101–108; 2001.
Ding, S.-T.; Schinckel, A. P.; Weber, T. E.; Mersmann, H. J. Expression of porcine transcription factors and genes related to fatty acid metabolism in different tissues and genetic populations J. Anim. Sci. 78:2127–2134; 2000a.
Distel, R. J.; Robinson, G. S.; Spiegelman, B. M. Fatty acid regulation of gene expression. J. Biol. Chem. 267:5937–5941; 1992.
Evans, M.; Geigerman, C.; Cook, J.; Curtis, L.; Kuebler, B.; McIntosh, M. Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3t3-l1 preadipocytes. Lipids 35:899–910; 2000.
Evans, M.; Park, Y.; Pariza, M.; Curtis, L.; Kuebler, B.; McIntosh, M. Trans-10, cis-12 conjugated linoleic acid reduces triglyceride content while differentially affecting peroxisome proliferator activated receptor gamma2 and ap2 expression in 3t3-l1 preadipocytes. Lipids 36:1223–1232; 2001.
Fajas, L.; Fruchart, J. C.; Auwerx, J. Transcriptional control of adipogenesis. Curr. Opin. Cell Biol. 10:165–173; 1998.
Gondret, F.; Ferre, P.; Dugail, I. Add-1/srebp-1 is a major determinant of tissue differential lipogenic capacity in mammalian and avian species. J. Lipid Res. 42:106–113; 2001.
Gregoire, F. M. Adipocyte differentiation: from fibroblast to endocrine cell. Exp. Biol. Med. (Maywood) 226:997–1002; 2001.
Gregoire, F. M.; Smas, C. M.; Sul, H. S. Understanding adipocyte differentiation. Physiol. Rev. 78:783–809; 1998.
Hannah, V. C.; Ou, J.; Luong, A.; Goldstein, J. L.; Brown, M. S. Unsaturated fatty acids down-regulate srebp isoforms 1a and 1c by two mechanisms in hek-293 cells. J. Biol. Chem. 276:4365–4372; 2001.
Hill, J. O.; Peters, J. C.; Lin, D.; Yakubu, F.; Greene, H.; Swift, L. Lipid accumulation and body fat distribution is influenced by type of dietary fat fed to rats. Int. J. Obeset. Relat. Metab. Disord. 17:223–236; 1993.
Houseknecht, K. L.; Vanden Heuvel, J. P.; Moya-Camarena, S. Y.; Portocarrero, C. P.; Peck, L. W.; Nickel, K. P.; Belury, M. A. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the zucker diabetic fatty fa/fa rat [published erratum appears in Biochem. Biophys. Res. Commun. 247(3):911; June 29; 1998]. Biochem. Biophys. Res. Commun. 244:678–682; 1998.
Kim, H. S.; Hausman, G. J.; Hausman, D. B.; Martin, R. J.; Dean, R. G. The expression of peroxisome proliferator-activated receptor gamma in pig fetal tissue and primary stromal-vascular cultures. Obes. Res. 8:83–88; 2000.
Kim, J. B.; Spiegelman, B. M. Add1/srebp1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 10:1096–1107; 1996.
Kim, H. J.; Takahashi, M.; Ezaki, O. Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (srebp-1) by down-regulation of srebp-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mRNAs. J. Biol. Chem. 274:25892–25898; 1999.
Kim, J. B.; Wright, H. M.; Wright, M.; Spiegelman, B. M. Add1/srebp1 activates ppargamma through the production of endogenous ligand. Proc. Natl. Acad. Sci. USA 95:4333–4337; 1998.
Kliewer, S. A.; Sundseth, S. S.; Jones, S. A., et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc. Natl. Acad. Sci. USA 94:4318–4323; 1997.
Krey, G.; Braissant, O.; L'Horset, F.; Kalkhoven, E.; Perroud, M.; Parker, M. G.; Wahli, W. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol. Endocrinol. 11:779–791; 1997.
Lee, K.; Hausman, G. J.; Dean, R. G. Expression of c/ebp alpha, beta and delta in fetal and postnatal subcutaneous adipose tissue. Mol. Cell. Biochem. 178:269–274; 1998.
MacDougald, O. A.; Mandrup, S. Adipogenesis: forces that tip the scales. Trends Endocrinol. Metab. 13:5–11; 2002.
Mandrup, S.; Lane, M. D. Regulating adipogenesis. J. Biol. Chem. 272:5367–5370; 1997.
McNeel, R. L.; Ding, S.; O'Brian Smith, E.; Mersmann, H. J. Expression of porcine adipocyte transcripts during differentiation in vitro and in vivo. Comp. Biochem. Physiol. B 126:291–302; 2000a.
McNeel, R. L.; Ding, S. T.; Smith, E. O.; Mersmann, H. J. Expression of porcine adipocyte transcripts during differentiation in vitro and in vivo. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 126:291–302; 2000b.
McNeel, R. L.; Mersmann, H. J. Distribution and quantification of beta1-, beta2-, and beta3-adrenergic receptor subtype transcripts in porcine tissues. J. Anim. Sci. 77:611–621; 1999.
Mersmann, H. J.; Goodman, J. R.; Brown, L. J. Development of swine adipose tissue: morphology and chemical composition. J. Lipid Res. 16:269–279; 1975.
Morrison, R. F.; Farmer, S. R. Insights into the transcriptional control of adipocyte differentiation. J. Cell. Biochem. Suppl.: 59–67; 1999.
O'Hea, E. K.; Leveille, G. A. Significance of adipose tissue and liver as sites of fatty acid synthesis in the pig and the efficiency of utilization of various substrates for lipogenesis. J. Nutr. 99:338–344; 1969.
Ostrowska, E.; Muralitharan, M.; Cross, R. F.; Bauman, D. E.; Dunshea, F. R. Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs. J. Nutr. 129:2037–2042; 1999.
Pariza, M. W.; Park, Y.; Cook, M. E. Mechanisms of action of conjugated linoleic acid: evidence and speculation. Proc. Soc. Exp. Biol. Med. 223:8–13; 2000.
Ramirez-Zacarias, J. L.; Castro-Munozledo, F.; Kuri-Harcuch, W. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red o. Histochemistry 97:493–497; 1992.
Ramsay, T. G.; Rao, S. V.; Wolverton, C. K. In vitro systems for the analysis of the development of adipose tissue in domestic animals. J. Nutr. 122:806–817; 1992.
Rosen, E. D.; Spiegelman, B. M. Molecular regulation of adipogenesis. Annu. Rev. Cell Dev. Biol. 16:145–171; 2000.
Rosen, E. D.; Walkey, C. J.; Puigserver, P.; Spiegelman, B. M. Transcriptional regulation of adipogenesis. Genes Dev. 14:1293–1307; 2000.
Sakai, J.; Duncan, E. A.; Rawson, R. B.; Hua, X.; Brown, M. S.; Goldstein, J. L. Sterol-regulated release of srebp-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell 85:1037–1046; 1996.
Satory, D. L.; Smith, S. B. Conjugated linoleic acid inhibits proliferation but stimulates lipid filling of murine 3t3-l1 preadipocytes. J. Nutr. 129:92–97; 1999.
Suryawan, A.; Hu, C. Y. Effect of serum on differentiation of porcine adipose stromal-vascular cells in primary culture. Comp. Biochem. Physiol. Comp. Physiol. 105:485–492; 1993.
Thoennes, S. R.; Tate, P. L.; Price, T. M.; Kilgore, M. W. Differential transcriptional activation of peroxisome proliferator-activated receptor gamma by omega-3 and omega-6 fatty acids in mcf-7 cells. Mol. Cell. Endocrinol. 160:67–73; 2000.
Tontonoz, P.; Hu, E.; Spiegelman, B. M. Stimulation of adipogenesis in fibroblasts by ppar gamma 2, a lipid-activated transcription factor [published erratum appears in Cell 80(6):Following 957; March 24, 1995]. Cell 79:1147–1156; 1994.
Xu, J.; Nakamura, M. T.; Cho, H. P.; Clarke, S. D. Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats. J. Biol. Chem. 274:23577–23583; 1999.
Xu, J.; Teran-Garcia, M.; Park, J. H.; Nakamura, M. T.; Clarke, S. D. Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay. J. Biol. Chem. 276:9800–9807; 2001.
Yahagi, N.; Shimano, H.; Hasty, A. H., et al. A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids. J. Biol. Chem. 274:35840–35844; 1999.
Yu, Z. K.; Hausman, G. J. Expression of ccaat/enhancer binding protein during porcine preadipocyte differentiation. Exp. Cell Res. 245:343–349; 1998.
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Ding, ST., McNeel, R.L. & Mersmann, H.J. Modulation of adipocyte determination and differentiation-dependent factor 1 by selected polyunsaturated fatty acids. In Vitro Cell.Dev.Biol.-Animal 38, 352–357 (2002). https://doi.org/10.1290/1071-2690(2002)038<0352:MOADAD>2.0.CO;2
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DOI: https://doi.org/10.1290/1071-2690(2002)038<0352:MOADAD>2.0.CO;2