DOI: 10.1101/gad.10.8.974. Differential activation of adipogenesis by multiple PPAR isoforms.

Differential activation of adipogenesis by multiple PPAR isoforms.

10.1101/gad.10.8.974

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor expressed predominantly in adipose tissue, where it plays a central role in the control of adipocyte gene expression and differentiation. Because there are two additional PPAR isoforms, PPARalpha and PPARdelta, and these are also expressed at some level in certain adipose depots, we have compared directly the adipogenic potential of all three receptors. Ectopically expressed PPARgamma powerfully induces adipogenesis at a morphological and molecular level in response to a number of PPARgamma activators. PPARalpha is less adipogenic but is able to induce significant differentiation in response to strong PPARalpha activators. Expression and activation of PPARdelta did not stimulate adipogenesis. Of the three PPARs, only PPARgamma can cooperate with C/EBPalpha in the promotion of adipogenesis. To begin to investigate the functional basis for the differential adipogenic activity of the PPAR isoforms, we have examined their ability to bind to several PPAR DNA response sequences. Compared with PPARalpha and PPARdelta, PPARgamma shows preferential binding to two well-characterized regulatory sequences derived from a fat-specific gene, ARE6 and ARE7. These data strongly suggest that PPARgamma is the predominant receptor regulating adipogenesis; however, they also suggest that PPARalpha may play a role in differentiation of certain adipose depots in response to a different set of physiologic activators or in certain disease states.

Bibliography

Brun, R. P., Tontonoz, P., Forman, B. M., Ellis, R., Chen, J., Evans, R. M., & Spiegelman, B. M. (1996). Differential activation of adipogenesis by multiple PPAR isoforms. Genes & Development, 10(8), 974â984.

Authors 7

R P Brun (first)
P Tontonoz (additional)
B M Forman (additional)
R Ellis (additional)
J Chen (additional)
R M Evans (additional)
B M Spiegelman (additional)

References 48 Referenced 374

10.1074/jbc.270.5.2367
10.1098/rspb.1992.0012 / Proc. R. Soc. Lond. Ser. B: Biol. Sci. / The ontogeny of peroxisome proliferator-activated receptor gene expression in mouse and rat. (1992)
10.1101/gad.5.9.1538
10.1016/0167-4889(91)90201-8 / Biochim. Biophys. Acta / Autocrine control of adipose cell differentiation by prostacyclin and PGF2a. (1991)
10.1021/bi00591a005
10.1101/gad.3.9.1323
10.1073/pnas.88.6.2593
10.1146/annurev.nu.14.070194.000531
10.1016/0003-2697(84)90381-6
10.1016/0092-8674(95)90193-0
10.1101/gad.8.14.1654
10.1073/pnas.89.10.4653
10.1101/gad.5.3.428
{'key': '2021111418294284000_10.8.974.14', 'first-page': '1202', 'article-title': 'Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression. (1992)
10.1016/0092-8674(74)90126-3
10.1016/0092-8674(76)90260-9
10.1073/pnas.91.23.11012
{'key': '2021111418294284000_10.8.974.18', 'first-page': '5331', 'article-title': 'A direct role for C/EBP and the AP-1 binding site in gene expression linked to adipocyte differentiation.', 'volume': '9', 'year': '1989', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / A direct role for C/EBP and the AP-1 binding site in gene expression linked to adipocyte differentiation. (1989)
10.1073/pnas.92.21.9856
10.1038/347645a0
10.1073/pnas.90.6.2160
10.1073/pnas.91.15.7355
10.1016/0092-8674(95)90194-9
10.1210/me.9.2.219
10.1093/nar/19.14.3998
10.1128/MCB.15.6.3012 / Mol. Cell. Biol. / Targeted disruption of the α-isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferates. (1995)
10.1074/jbc.270.22.12953
10.1073/pnas.91.19.8757
Maniatis, T., E.F. Fritsch, and J. Sambrook. 1989. Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
10.1016/S0021-9258(17)36979-X / J. Biol. Chem. / cDNA cloning of a mouse prostacyclin receptor. Multiple signaling pathways and expression in thymic medulla. (1994)
{'key': '2021111418294284000_10.8.974.31', 'first-page': '17297', 'article-title': 'Differentiation induced gene expression in 3T3-L1 preadipocytes.', 'volume': '263', 'year': '1988', 'journal-title': 'J. Biol. Chem.'} / J. Biol. Chem. / Differentiation induced gene expression in 3T3-L1 preadipocytes. (1988)
{'key': '2021111418294284000_10.8.974.32', 'first-page': '6264', 'article-title': 'The role of the CAAT/enhancer-binding protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP).', 'volume': '10', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The role of the CAAT/enhancer-binding protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP). (1990)
10.1073/pnas.90.18.8392
10.1073/pnas.87.24.9590
10.1002/j.1460-2075.1991.tb04948.x / EMBO J. / The CAAT/enhancer binding protein and its role in adipocyte differentiation: Evidence for direct involvement in terminal adipocyte development. (1991)
10.1210/me.6.10.1634
10.1074/jbc.270.47.28183
10.1101/gad.8.10.1224
10.1093/nar/22.25.5628
10.1016/0092-8674(94)90006-X
10.1128/MCB.15.1.351 / Mol. Cell. Biol. / PPARγ2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. (1995)
10.1002/j.1460-2075.1992.tb05072.x / EMBO J. / The mouse peroxisomal proliferator activated receptor recognizes a response element in the 5′ flanking sequence of the rat acyl CoA oxidase gene. (1992)
10.1126/science.1987644
10.1016/S0021-9258(19)49879-7 / J. Biol. Chem. / Prostacyclin is a specific effector of adipose cell differentiation. Its dual role as a cAMP and Ca2--elevating agent. (1992)
10.1101/gad.9.19.2350
10.1101/gad.9.2.168
10.1074/jbc.270.41.23975
10.1073/pnas.92.17.7921

Dates

Type	When
Created	18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 9:47 p.m.)
Indexed	3 weeks, 4 days ago (Aug. 6, 2025, 8:16 a.m.)
Issued	29 years, 4 months ago (April 15, 1996)
Published	29 years, 4 months ago (April 15, 1996)
Published Online	29 years, 4 months ago (April 15, 1996)
Published Print	29 years, 4 months ago (April 15, 1996)

Funders 0

None

BibTeX

@article{Brun_1996, title={Differential activation of adipogenesis by multiple PPAR isoforms.}, volume={10}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.10.8.974}, DOI={10.1101/gad.10.8.974}, number={8}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Brun, R P and Tontonoz, P and Forman, B M and Ellis, R and Chen, J and Evans, R M and Spiegelman, B M}, year={1996}, month=apr, pages={974–984} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        6
      ]
    ],
    "date-time": "2025-08-06T12:16:59Z",
    "timestamp": 1754482619058
  },
  "reference-count": 48,
  "publisher": "Cold Spring Harbor Laboratory",
  "issue": "8",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1996,
        4,
        15
      ]
    ]
  },
  "abstract": "<jats:p>Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor expressed predominantly in adipose tissue, where it plays a central role in the control of adipocyte gene expression and differentiation. Because there are two additional PPAR isoforms, PPARalpha and PPARdelta, and these are also expressed at some level in certain adipose depots, we have compared directly the adipogenic potential of all three receptors. Ectopically expressed PPARgamma powerfully induces adipogenesis at a morphological and molecular level in response to a number of PPARgamma activators. PPARalpha is less adipogenic but is able to induce significant differentiation in response to strong PPARalpha activators. Expression and activation of PPARdelta did not stimulate adipogenesis. Of the three PPARs, only PPARgamma can cooperate with C/EBPalpha in the promotion of adipogenesis. To begin to investigate the functional basis for the differential adipogenic activity of the PPAR isoforms, we have examined their ability to bind to several PPAR DNA response sequences. Compared with PPARalpha and PPARdelta, PPARgamma shows preferential binding to two well-characterized regulatory sequences derived from a fat-specific gene, ARE6 and ARE7. These data strongly suggest that PPARgamma is the predominant receptor regulating adipogenesis; however, they also suggest that PPARalpha may play a role in differentiation of certain adipose depots in response to a different set of physiologic activators or in certain disease states.</jats:p>",
  "DOI": "10.1101/gad.10.8.974",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2007,
        6,
        5
      ]
    ],
    "date-time": "2007-06-05T21:15:46Z",
    "timestamp": 1181078146000
  },
  "page": "974-984",
  "source": "Crossref",
  "is-referenced-by-count": 374,
  "title": "Differential activation of adipogenesis by multiple PPAR isoforms.",
  "prefix": "10.1101",
  "volume": "10",
  "author": [
    {
      "given": "R P",
      "family": "Brun",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "P",
      "family": "Tontonoz",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "B M",
      "family": "Forman",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "R",
      "family": "Ellis",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "J",
      "family": "Chen",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "R M",
      "family": "Evans",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "B M",
      "family": "Spiegelman",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "246",
  "published-online": {
    "date-parts": [
      [
        1996,
        4,
        15
      ]
    ]
  },
  "reference": [
    {
      "key": "2021111418294284000_10.8.974.1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.5.2367"
    },
    {
      "key": "2021111418294284000_10.8.974.2",
      "doi-asserted-by": "crossref",
      "first-page": "83",
      "DOI": "10.1098/rspb.1992.0012",
      "article-title": "The ontogeny of peroxisome proliferator-activated receptor gene expression in mouse and rat.",
      "volume": "247",
      "year": "1992",
      "journal-title": "Proc. R. Soc. Lond. Ser. B:  Biol. Sci."
    },
    {
      "key": "2021111418294284000_10.8.974.3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.5.9.1538"
    },
    {
      "key": "2021111418294284000_10.8.974.4",
      "doi-asserted-by": "crossref",
      "first-page": "364",
      "DOI": "10.1016/0167-4889(91)90201-8",
      "article-title": "Autocrine control of adipose cell differentiation by prostacyclin and PGF2a.",
      "volume": "1091",
      "year": "1991",
      "journal-title": "Biochim. Biophys. Acta"
    },
    {
      "key": "2021111418294284000_10.8.974.5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00591a005"
    },
    {
      "key": "2021111418294284000_10.8.974.6",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.3.9.1323"
    },
    {
      "key": "2021111418294284000_10.8.974.7",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.88.6.2593"
    },
    {
      "key": "2021111418294284000_10.8.974.8",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.nu.14.070194.000531"
    },
    {
      "key": "2021111418294284000_10.8.974.9",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0003-2697(84)90381-6"
    },
    {
      "key": "2021111418294284000_10.8.974.10",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90193-0"
    },
    {
      "key": "2021111418294284000_10.8.974.11",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.8.14.1654"
    },
    {
      "key": "2021111418294284000_10.8.974.12",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.89.10.4653"
    },
    {
      "key": "2021111418294284000_10.8.974.13",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.5.3.428"
    },
    {
      "key": "2021111418294284000_10.8.974.14",
      "first-page": "1202",
      "article-title": "Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression.",
      "volume": "12",
      "year": "1992",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2021111418294284000_10.8.974.15",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(74)90126-3"
    },
    {
      "key": "2021111418294284000_10.8.974.16",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(76)90260-9"
    },
    {
      "key": "2021111418294284000_10.8.974.17",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.23.11012"
    },
    {
      "key": "2021111418294284000_10.8.974.18",
      "first-page": "5331",
      "article-title": "A direct role for C/EBP and the AP-1 binding site in gene expression linked to adipocyte differentiation.",
      "volume": "9",
      "year": "1989",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2021111418294284000_10.8.974.19",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.21.9856"
    },
    {
      "key": "2021111418294284000_10.8.974.20",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/347645a0"
    },
    {
      "key": "2021111418294284000_10.8.974.21",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.6.2160"
    },
    {
      "key": "2021111418294284000_10.8.974.22",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.15.7355"
    },
    {
      "key": "2021111418294284000_10.8.974.23",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90194-9"
    },
    {
      "key": "2021111418294284000_10.8.974.24",
      "doi-asserted-by": "publisher",
      "DOI": "10.1210/me.9.2.219"
    },
    {
      "key": "2021111418294284000_10.8.974.25",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/19.14.3998"
    },
    {
      "key": "2021111418294284000_10.8.974.26",
      "doi-asserted-by": "crossref",
      "first-page": "3012",
      "DOI": "10.1128/MCB.15.6.3012",
      "article-title": "Targeted disruption of the \u03b1-isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferates.",
      "volume": "15",
      "year": "1995",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2021111418294284000_10.8.974.27",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.22.12953"
    },
    {
      "key": "2021111418294284000_10.8.974.28",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.19.8757"
    },
    {
      "key": "2021111418294284000_10.8.974.29",
      "unstructured": "Maniatis, T., E.F. Fritsch, and J. Sambrook. 1989. Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY."
    },
    {
      "key": "2021111418294284000_10.8.974.30",
      "doi-asserted-by": "crossref",
      "first-page": "9986",
      "DOI": "10.1016/S0021-9258(17)36979-X",
      "article-title": "cDNA cloning of a mouse prostacyclin receptor. Multiple signaling pathways and expression in thymic medulla.",
      "volume": "269",
      "year": "1994",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2021111418294284000_10.8.974.31",
      "first-page": "17297",
      "article-title": "Differentiation induced gene expression in 3T3-L1 preadipocytes.",
      "volume": "263",
      "year": "1988",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2021111418294284000_10.8.974.32",
      "first-page": "6264",
      "article-title": "The role of the CAAT/enhancer-binding protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP).",
      "volume": "10",
      "year": "1990",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2021111418294284000_10.8.974.33",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.18.8392"
    },
    {
      "key": "2021111418294284000_10.8.974.34",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.87.24.9590"
    },
    {
      "key": "2021111418294284000_10.8.974.35",
      "doi-asserted-by": "crossref",
      "first-page": "3787",
      "DOI": "10.1002/j.1460-2075.1991.tb04948.x",
      "article-title": "The CAAT/enhancer binding protein and its role in adipocyte differentiation: Evidence for direct involvement in terminal adipocyte development.",
      "volume": "10",
      "year": "1991",
      "journal-title": "EMBO J."
    },
    {
      "key": "2021111418294284000_10.8.974.36",
      "doi-asserted-by": "publisher",
      "DOI": "10.1210/me.6.10.1634"
    },
    {
      "key": "2021111418294284000_10.8.974.37",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.47.28183"
    },
    {
      "key": "2021111418294284000_10.8.974.38",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.8.10.1224"
    },
    {
      "key": "2021111418294284000_10.8.974.39",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/22.25.5628"
    },
    {
      "key": "2021111418294284000_10.8.974.40",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(94)90006-X"
    },
    {
      "key": "2021111418294284000_10.8.974.41",
      "doi-asserted-by": "crossref",
      "first-page": "351",
      "DOI": "10.1128/MCB.15.1.351",
      "article-title": "PPAR\u03b32 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene.",
      "volume": "15",
      "year": "1995",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2021111418294284000_10.8.974.42",
      "doi-asserted-by": "crossref",
      "first-page": "433",
      "DOI": "10.1002/j.1460-2075.1992.tb05072.x",
      "article-title": "The mouse peroxisomal proliferator activated receptor recognizes a response element in the 5\u2032 flanking sequence of the rat acyl CoA oxidase gene.",
      "volume": "11",
      "year": "1992",
      "journal-title": "EMBO J."
    },
    {
      "key": "2021111418294284000_10.8.974.43",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1987644"
    },
    {
      "key": "2021111418294284000_10.8.974.44",
      "doi-asserted-by": "crossref",
      "first-page": "11092",
      "DOI": "10.1016/S0021-9258(19)49879-7",
      "article-title": "Prostacyclin is a specific effector of adipose cell differentiation. Its dual role as a cAMP and Ca2--elevating agent.",
      "volume": "267",
      "year": "1992",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2021111418294284000_10.8.974.45",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.9.19.2350"
    },
    {
      "key": "2021111418294284000_10.8.974.46",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.9.2.168"
    },
    {
      "key": "2021111418294284000_10.8.974.47",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.41.23975"
    },
    {
      "key": "2021111418294284000_10.8.974.48",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.17.7921"
    }
  ],
  "container-title": "Genes &amp; Development",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://syndication.highwire.org/content/doi/10.1101/gad.10.8.974",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2021,
        11,
        15
      ]
    ],
    "date-time": "2021-11-15T02:47:50Z",
    "timestamp": 1636944470000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "http://genesdev.cshlp.org/lookup/doi/10.1101/gad.10.8.974"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1996,
        4,
        15
      ]
    ]
  },
  "references-count": 48,
  "journal-issue": {
    "issue": "8",
    "published-print": {
      "date-parts": [
        [
          1996,
          4,
          15
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1101/gad.10.8.974"
  ],
  "URL": "http://dx.doi.org/10.1101/gad.10.8.974",
  "relation": {},
  "ISSN": [
    "0890-9369",
    "1549-5477"
  ],
  "subject": [],
  "container-title-short": "Genes Dev.",
  "published": {
    "date-parts": [
      [
        1996,
        4,
        15
      ]
    ]
  }
}