Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans
Tumor suppressor candidate 5 (TUSC5) is a gene expressed abundantly in white adipose tissue (WAT), brown adipose tissue (BAT), and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ) agonist treatment of 3T3...
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| Language: | English |
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Wiley
2009-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2009/867678 |
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| author | Trina A. Knotts Hyun Woo Lee Jae Bum Kim Pieter J. Oort Ruth McPherson Robert Dent Keisuke Tachibana Takefumi Doi Songtao Yu Janardan K. Reddy Kenji Uno Hideki Katagiri Magdalena Pasarica Steven R. Smith Dorothy D. Sears Michel Grino Sean H. Adams |
| author_facet | Trina A. Knotts Hyun Woo Lee Jae Bum Kim Pieter J. Oort Ruth McPherson Robert Dent Keisuke Tachibana Takefumi Doi Songtao Yu Janardan K. Reddy Kenji Uno Hideki Katagiri Magdalena Pasarica Steven R. Smith Dorothy D. Sears Michel Grino Sean H. Adams |
| author_sort | Trina A. Knotts |
| collection | DOAJ |
| description | Tumor suppressor candidate 5 (TUSC5) is a gene expressed abundantly in white adipose tissue (WAT), brown adipose tissue (BAT), and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ) agonist treatment of 3T3-L1 adipocytes suggested a role for Tusc5 in fat cell proliferation and/or metabolism. However, the regulation of Tusc5 in WAT and its potential association with obesity phenotypes remain unclear. We tested the hypothesis that the TUSC5 gene is a bona fide PPARγ target and evaluated whether its WAT expression or single-nucleotide polymorphisms (SNPs) in the TUSC5 coding region are associated with human obesity. Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitazone and GW1929 followed a dose-response consistent with these agents' binding affinities for PPARγ. Chromatin immunoprecipitation (ChIP) experiments confirmed that PPARγ protein binds a ∼−1.1 kb promotor sequence of murine TUSC5 transiently during 3T3-L1 adipogenesis, concurrent with histone H3 acetylation. No change in Tusc5 mRNA or protein levels was evident in type 2 diabetic patients treated with pioglitazone. Tusc5 expression was not induced appreciably in liver preparations overexpressing PPARs, suggesting that tissue-specific factors regulate PPARγ responsiveness of the TUSC5 gene. Finally, we observed no differences in Tusc5 WAT expression or prevalence of coding region SNPs in lean versus obese human subjects. These studies firmly establish the murine TUSC5 gene locus as a PPARγ target, but the significance of Tusc5 in obesity phenotypes or in the pharmacologic actions of PPARγ agonists in humans remains equivocal. |
| format | Article |
| id | doaj-art-f35ddad14fe04e7797cd00ff2702b87c |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
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| series | PPAR Research |
| spelling | doaj-art-f35ddad14fe04e7797cd00ff2702b87c2025-02-03T01:02:00ZengWileyPPAR Research1687-47571687-47652009-01-01200910.1155/2009/867678867678Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese HumansTrina A. Knotts0Hyun Woo Lee1Jae Bum Kim2Pieter J. Oort3Ruth McPherson4Robert Dent5Keisuke Tachibana6Takefumi Doi7Songtao Yu8Janardan K. Reddy9Kenji Uno10Hideki Katagiri11Magdalena Pasarica12Steven R. Smith13Dorothy D. Sears14Michel Grino15Sean H. Adams16Obesity & Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA 95616, USADepartment of Biological Sciences, Department of Biophysics and Chemical Biology, Seoul National University, Seoul 151-742, South KoreaDepartment of Biological Sciences, Department of Biophysics and Chemical Biology, Seoul National University, Seoul 151-742, South KoreaObesity & Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA 95616, USADivision of Cardiology, University of Ottawa Heart Institute, Ottawa, K1H 8L1, CanadaDivision of Cardiology, University of Ottawa Heart Institute, Ottawa, K1H 8L1, CanadaGraduate Schools of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, JapanGraduate Schools of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, JapanDepartment of Pathology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60208, USADepartment of Pathology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60208, USADivision of Advanced Therapeutics for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8576, JapanDivision of Advanced Therapeutics for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8576, JapanPennington Biomedical Research Center, Baton Rouge, LA 70808, USAPennington Biomedical Research Center, Baton Rouge, LA 70808, USADepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USAInstitute National de la Santé et de la Recherche Médicale (INSERM) UMR 626, 13385 Marseille and Faculté de Médecine, Université de la Méditerranée, Marseille, FranceObesity & Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, CA 95616, USATumor suppressor candidate 5 (TUSC5) is a gene expressed abundantly in white adipose tissue (WAT), brown adipose tissue (BAT), and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ) agonist treatment of 3T3-L1 adipocytes suggested a role for Tusc5 in fat cell proliferation and/or metabolism. However, the regulation of Tusc5 in WAT and its potential association with obesity phenotypes remain unclear. We tested the hypothesis that the TUSC5 gene is a bona fide PPARγ target and evaluated whether its WAT expression or single-nucleotide polymorphisms (SNPs) in the TUSC5 coding region are associated with human obesity. Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitazone and GW1929 followed a dose-response consistent with these agents' binding affinities for PPARγ. Chromatin immunoprecipitation (ChIP) experiments confirmed that PPARγ protein binds a ∼−1.1 kb promotor sequence of murine TUSC5 transiently during 3T3-L1 adipogenesis, concurrent with histone H3 acetylation. No change in Tusc5 mRNA or protein levels was evident in type 2 diabetic patients treated with pioglitazone. Tusc5 expression was not induced appreciably in liver preparations overexpressing PPARs, suggesting that tissue-specific factors regulate PPARγ responsiveness of the TUSC5 gene. Finally, we observed no differences in Tusc5 WAT expression or prevalence of coding region SNPs in lean versus obese human subjects. These studies firmly establish the murine TUSC5 gene locus as a PPARγ target, but the significance of Tusc5 in obesity phenotypes or in the pharmacologic actions of PPARγ agonists in humans remains equivocal.http://dx.doi.org/10.1155/2009/867678 |
| spellingShingle | Trina A. Knotts Hyun Woo Lee Jae Bum Kim Pieter J. Oort Ruth McPherson Robert Dent Keisuke Tachibana Takefumi Doi Songtao Yu Janardan K. Reddy Kenji Uno Hideki Katagiri Magdalena Pasarica Steven R. Smith Dorothy D. Sears Michel Grino Sean H. Adams Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans PPAR Research |
| title | Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans |
| title_full | Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans |
| title_fullStr | Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans |
| title_full_unstemmed | Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans |
| title_short | Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans |
| title_sort | molecular characterization of the tumor suppressor candidate 5 gene regulation by pparγ and identification of tusc5 coding variants in lean and obese humans |
| url | http://dx.doi.org/10.1155/2009/867678 |
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