The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone
Abstract
The objective of this study was to further establish and confirm the relationship of adipose mitochondrial biogenesis in diabetes/obesity and the effects of rosiglitazone (RSG), a peroxisome proliferator-activated receptor (PPAR) gamma agonist, by systematically analyzing mitochondrial gene expression and function in two mouse models of obesity and type 2 diabetes. Using microarray technology, adipose mitochondrial gene transcription was studied in db/db, high-fat diet-fed C57BL/6 (HFD) and respective control mice with or without RSG treatment. The findings were extended using mitochondrial staining, DNA quantification, and measurements of citrate synthase activity. In db/db and HFD mice, gene transcripts associated with mitochondrial ATP production, energy uncoupling, mitochondrial ribosomal proteins, outer and inner membrane translocases, and mitochondrial heat-shock proteins were decreased in abundance, compared with db/+ and standard-fat diet-fed control mice, respectively. RSG dose-dependently increased these transcripts in both db/db and HFD mice and induced transcription of mitochondrial structural proteins and cellular antioxidant enzymes responsible for removal of reactive oxygen species generated by increased mitochondrial activity. Transcription factors, including PPAR coactivator (PGC)-1beta, PGC-1alpha, estrogen-related receptor alpha, and PPARalpha, were suppressed in both models and induced by RSG. The effects of RSG on adipose mitochondrial genes were confirmed by quantitative RT-PCR and further supported by mitochondrial staining, mitochondrial DNA quantification, and citrate synthase activity. Adipose mitochondrial biogenesis was overwhelmingly suppressed in both mouse models of diabetes/obesity and globally induced by RSG. These findings suggest an important role of adipose mitochondria in diabetes/obesity and the potential for new treatment approaches targeting adipose mitochondria.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Administration of thiazolidinediones induces changes in mitochondrial content and remodeling in white adipocytes concomitantly with an improvement in insulin sensitivity (170, 173, 177, 190, 194 -198).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [190]
In the citing paper
“Conversely, both genetic and dietinduced obesity result in decreased mitochondrial density and OXPHOS activity in adipose tissue (127, 177, 189 -191), potentially contributing to adipose tissue dysfunction and exacerbation of insulin resistance.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [190]
In the citing paper
“White adipocyte mitochondrial content is decreased in both rodent and human obesity (177, 188 -191) and correlates with insulin resistance that accompanies obesity.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [190]
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes
Scherer, P. E., Williams, S. P., Fogliano, M., Baldini, G., & Lodish, H. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26746 · Cited by 3,238
Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome
Kadowaki, T. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29126 · Cited by 2,824
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546
Reactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525 · cited 1×
“A recent study (46) also showed upregulation of antioxidant enzymes per se may be beneficial for improving insulin resistance.”
BackgroundAbnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321
Metabolic control through the PGC-1 family of transcription coactivators
Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130 · cited 2×
“The dual RSG actions on mitochondria and antioxidant enzymes could work through the upregulation of one or both of the PGC-1 proteins (Table 3) that have been shown to regulate both mitochondrial biogenesis and the antioxidant machinery (13,45).”
BackgroundPatti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677
PPARs and the complex journey to obesity
Evans, R. M., Barish, G. D., & Wang, Y.-X. (2004) · Nature Medicine · doi:10.1038/nm1025 · Cited by 1,650
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., Charo, I., Leibel, R. L., & Jr., A. W. F. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335 · Cited by 1,497
Lehrke, M., & Lazar, M. A. (2005) · Cell · doi:10.1016/j.cell.2005.11.026 · Cited by 1,472
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335c1 · Cited by 1,425
Mootha, V. K., Bunkenborg, J., Olsen, J. V., Hjerrild, M., Wisniewski, J. R., Stahl, E., Bolouri, M. S., Ray, H. N., Sihag, S., Kamal, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00926-7 · Cited by 889
Cinti, S. (2005) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2005.04.010 · Cited by 720
The mitochondrial uncoupling-protein homologues
Krauss, S., Zhang, C., & Lowell, B. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1592 · Cited by 670
Uldry, M., Yang, W., St‐Pierre, J., Lin, J. D., Seale, P., & Spiegelman, B. M. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.002 · Cited by 651
Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N., Rizza, R. A., Coenen-Schimke, J. M., & Nair, K. S. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1888 · Cited by 631
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
Wilson-Fritch, L., Nicoloro, S., Chouinard, M., Lazar, M. A., Chui, P. C., Leszyk, J., Straubhaar, J., Czech, M. P., & Corvera, S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21752 · Cited by 616
The Biology of Mitochondrial Uncoupling Proteins
Rousset, S., Alves‐Guerra, M., Mozo, J., Miroux, B., Cassard, A., Bouillaud, F., & Ricquier, D. (2004) · Diabetes · doi:10.2337/diabetes.53.2007.s130 · Cited by 560
St‐Pierre, J., Lin, J. D., Krauss, S., Tarr, P. T., Yang, R., Newgard, C. B., & Spiegelman, B. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301850200 · Cited by 554
Kopecky, J., Clarke, G., Enerbäck, S., Spiegelman, B., & Kozak, L. P. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118363 · Cited by 553
Cidea-deficient mice have lean phenotype and are resistant to obesity
Zhou, Z., Toh, S. Y., Chen, Z., Guo, K., Ng, C. P., Ponniah, S., Lin, S., Hong, W., & Li, P. (2003) · Nature Genetics · doi:10.1038/ng1225 · Cited by 468
Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo
Bogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1392 · Cited by 467
The Mitochondrial Inner Membrane Protein Mitofilin Controls Cristae Morphology
John, G. B., Shang, Y., Li, L., Renken, C. W., Mannella, C. A., Selker, J. M. L., Rangell, L. K., Bennett, M. J., & Zha, J. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-08-0697 · Cited by 459
Wilson-Fritch, L., Burkart, A., Bell, G., Mendelson, K., Leszyk, J., Nicoloro, S., Czech, M., & Corvera, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.1085-1094.2003 · Cited by 459
Olichon, A., Emorine, L. J., Descoins, E., Pelloquin, L., Brichese, L., Gas, N., Guillou, E., Delettre, C., Valette, A., Hamel, C., et al. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02985-x · Cited by 430
Arany, Z., Lebrasseur, N., Morris, C., Smith, E., Yang, W., Ma, Y., Chin, S., & Spiegelman, B. M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2006.12.003 · Cited by 370
Mitochondria are impaired in the adipocytes of type 2 diabetic mice.
Choo, H.-J., Kim, J.-H., Kwon, O.-B., Lee, C. S., Mun, J. Y., Han, S. S., Yoon, Y.-S., Yoon, G., Choi, K.-M., & Ko, Y.-G. (2006) · Diabetologia · doi:10.1007/s00125-006-0170-2 · Cited by 365
Visapää, I., Fellman, V., Vesa, J., Dasvarma, A., Hutton, J., Kumar, V., Payne, G. S., Makarow, M., Coster, R. V., Taylor, R. W., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342773 · Cited by 308
Lelliott, C. J., Medina-Gomez, G., Petrovic, N., Kis, A., Feldmann, H. M., Bjursell, M., Parker, N., Curtis, K., Campbell, M., Hu, P., et al. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040369 · Cited by 280 · cited 1×
“co-activators (PGC) 1α and 1β have been implicated as key regulators of mitochondrial biogenesis in adipose tissue (3,6,34-37) and muscle (11,36-40).”
BackgroundPowelka, A. M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26040 · Cited by 236
Rapid transformation of white adipocytes into fat-oxidizing machines
Orci, L., Cook, W. S., Ravazzola, M., Wang, M.-Y., Park, B.-H., Montesano, R., & Unger, R. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308258100 · Cited by 234
Meirhaeghe, A., Crowley, V., Lenaghan, C., Lelliott, C. J., GREEN, K., Stewart, A., Kevin, H. A. R. T., Schinner, S., Sethi, J. K., Yeo, G. S. H., et al. (2003) · Biochemical Journal · doi:10.1042/bj20030200 · Cited by 218
MacLellan, J. D., Gerrits, M. F., Gowing, A., Smith, P. J. S., Wheeler, M. B., & Harper, M.-E. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2343 · Cited by 213
Reversal of diet-induced obesity and diabetes in C57BL/6J mice
Parekh, P. I., Petro, A. E., Tiller, J. M., Feinglos, M. N., & Surwit, R. S. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90283-9 · Cited by 201
RIP140-Targeted Repression of Gene Expression in Adipocytes
Christian, M., Kiskinis, E., Debevec, D., Leonardsson, G., White, R., & Parker, M. G. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9383-9391.2005 · Cited by 184
Rosiglitazone Induces Mitochondrial Biogenesis in Mouse Brain
Strum, J. C., Shehee, R., Virley, D. J., Richardson, J. C., Mattie, M. D., Selley, P., Ghosh, S., Nock, C. M., Saunders, A. M., & Roses, A. D. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11108 · Cited by 183
Structural and Functional Consequences of Mitochondrial Biogenesis in Human Adipocytes in Vitro
Bogacka, I., Ukropcova, B., McNeil, M., Gimble, J. M., & Smith, S. R. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1024 · Cited by 138
Williams, S. L., Valnot, I., Rustin, P., & Taanman, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309232200 · Cited by 133
β-Adrenergic Receptors and Regulation of Energy Expenditure: A Family Affair
Robidoux, J., Martin, T. L., & Collins, S. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121659 · Cited by 132
BROWN, N. F., HILL, J. K., Esser, V., Kirkland, J. L., Corkey, B. E., Foster, D. W., & McGarry, J. (1997) · Biochemical Journal · doi:10.1042/bj3270225 · Cited by 114
Statistical Significance Threshold Criteria For Analysis of Microarray Gene Expression Data
Cheng, C., Pounds, S. B., Boyett, J. M., Pei, D., Kuo, M.-L., & Roussel, M. F. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1064 · Cited by 47
Receptor-activated Smad localisation in Bleomycin-induced pulmonary fibrosis
Higashiyama, H., Yoshimoto, D., Okamoto, Y., Kikkawa, H., Asano, S., & Kinoshita, M. (2006) · Journal of Clinical Pathology · doi:10.1136/jcp.2006.037606 · Cited by 40
Effects of Alzheimer's peptide and α1-antichymotrypsin on astrocyte gene expression
Baker, C., Nielsen, H. M., Minthon, L., Wright, H. T., Chappell, S., Okyere, J., May, S. T., Morgan, K., Kalsheker, N. A., & Janciauskiene, S. M. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.10.017 · Cited by 11
Flagged first, then by citations
Research works printed but not linked: 1
- Okamoto K, Higashiyama H, Rong JX, McVey MJ, Kinoshita M, Asano S, Hansen MH: Comparison of adipose mitochondria and macrophage content between subcutaneous and visceral adipose tissues in db/db mice and effects of rosiglitazone. Mol Exp Med. In press
Cited by
Sorted by citations
Brown and beige fat: Development, function and therapeutic potential
Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328
Bhatti, J. S., Bhatti, G. K., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.010 · Cited by 1,655
Petrovic, N., Walden, T. B., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.053942 · Cited by 1,263
PPARγ agonists Induce a White-to-Brown Fat Conversion through Stabilization of PRDM16 Protein
Ohno, H., Shinoda, K., Spiegelman, B. M., & Kajimura, S. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.019 · Cited by 770
PGC-1 α , Inflammation, and Oxidative Stress: An Integrative View in Metabolism
Rius‐Pérez, S., Torres-Cuevas, I., Millán, I., Ortega, Á., & Pérez, S. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1452696 · Cited by 671
Metadata
- Authors
- Rong, J. X., Qiu, Y., Hansen, M. K., Zhu, L., Zhang, V., Xie, M., Okamoto, Y., Mattie, M. D., Higashiyama, H., Asano, S., Strum, J. C., & Ryan, T. E.
- Affiliations
- High Throughput Biology, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
- GlaxoSmithKline (United States) (US)
- GlaxoSmithKline (Japan) (JP)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-07-01
- Volume
- 56
- Issue
- 7
- Pages
- 1751-1760
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2116872683
- Cited by
- 335
- References
- 48
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 17 · 2021: 13 · 2020: 21 · 2019: 19 · 2018: 16 · 2017: 23 · 2016: 27 · 2015: 23 · 2014: 27 · 2013: 23 · 2012: 17
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- rosiglitazone, type 2 diabetes, obesity, db/db mice, high-fat diet, PPARγ agonists, PGC-1α, PGC-1β, mitochondrial gene expression, mitochondrial DNA, citrate synthase, reactive oxygen species, antioxidant enzymes, mitochondrial uncoupling, mitochondrial heat shock proteins
- MeSH terms
- Rosiglitazone, Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Dietary Fats, Disease Models, Animal, Hypoglycemic Agents, Male, Mice, Inbred C57BL, Mitochondria, Obesity, Transcription, Genetic, Gene Expression, Gene Expression Profiling, Thiazolidinediones, PPAR gamma, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
