Structural and Functional Consequences of Mitochondrial Biogenesis in Human Adipocytes in Vitro
Abstract
INTRODUCTION: Mitochondrial biogenesis is a complex process, and several factors and signaling pathways regulate this process in muscle or brown adipocytes. The aim of the study was to explore pathways affecting mitochondrial biogenesis and fatty acid oxidation (FAO) in human white adipocytes. METHODS: Human preadipocytes obtained from liposuction samples were differentiated in vitro. On the 10th day of differentiation, 4 microM forskolin and 1 microM peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist (pioglitazone, rosiglitazone, or GW 929) or 10 microM PPARalpha agonist (WY-14,643) were added to the media for 96 h. Quantitative real-time PCR was used to determine gene expression/mitochondrial copy number and 14C-labeled palmitate to measure direct energy dissipation. RESULTS: The treatment of adipocytes with forskolin increased mitochondrial copy number and the expression of genes involved in mitochondrial biogenesis (PPARgamma coactivator 1alpha and transcriptional factor A) and fatty acid oxidation (PPARalpha and medium-chain acyl-coenzyme A dehydrogenase). The end (CO2) and intermediate products (14C-labeled acid-soluble products) of FAO were also increased after forskolin treatment. PPARgamma and PPARalpha agonists increased mitochondrial copy number, uncoupling protein 1, medium-chain acyl-coenzyme A dehydrogenase, and carnitine palmitoyltransferase 1, but did not change PPARalpha, PPARgamma coactivator 1alpha, or transcriptional factor A mRNA levels. FAO was higher after rosiglitazone, GW 929, and WY-14,643 but not after pioglitazone treatment. CONCLUSIONS: Pharmacological activation of the cAMP or PPARgamma pathway pushes the white adipocyte down the oxidative continuum. The direct energy-dissipating effects could be significant tools to treat obesity and to improve insulin resistance in type 2 diabetic patients by reduction of fat accumulation in adipocytes or by reprogramming fatty acid metabolism.
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Mitochondrial levels in white adipocytes are also increased in response to adrenergic stimulation, β-3 agonists, and CB1 blockade in mice, again in parallel with enhanced insulin sensitivity.
“Mitochondrial levels in white adipocytes are also increased in response to adrenergic stimulation, -3 agonists, and CB1 blockade in mice (195,199,200), again in parallel with enhanced insulin sensitivity.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [195]
Administration of thiazolidinediones induces changes in mitochondrial content and remodeling in white adipocytes concomitantly with an improvement in insulin sensitivity.
“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 [195]
Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · see citing works
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864 · see citing works
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193 · see citing works
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076 · see citing works
Patti, 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 · see citing works
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821 · see citing works
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
Herzig, S., Long, F., Jhala, U. S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., et al. (2001) · Nature · doi:10.1038/35093131 · Cited by 1,440 · see citing works
Transcriptional regulatory circuits controlling mitochondrial biogenesis and function
Kelly, D. P., & Scarpulla, R. C. (2004) · Genes & Development · doi:10.1101/gad.1177604 · Cited by 1,243 · see citing works
Vega, R. B., Huss, J. M., & Kelly, D. P. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1868-1876.2000 · Cited by 1,195 · see citing works
Hauner, H., Entenmann, G., Wabitsch, M., Gaillard, D., Ailhaud, G. P., Négrel, R., & Pfeiffer, E. F. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114345 · Cited by 621 · see citing works
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 · see citing works
Acquirement of brown fat cell features by human white adipocytes
Tiraby, C., Tavernier, G., Lefort, C., Larrouy, D., Bouillaud, F., Ricquier, D., & Langin, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305235200 · Cited by 474 · see citing works
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 · see citing works
Self-citationWilson-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 · see citing works
Peroxisome proliferator-activated receptor $gamma; in diabetes and metabolism
Rangwala, S. M., & Lazar, M. A. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.03.012 · Cited by 456 · see citing works
Russell, A. P., Feilchenfeldt, J. W., Schreiber, S., Praz, M., Crettenand, A., Gobelet, C., Meier, C. A., Bell, D., Kralli, A., Giacobino, J., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2874 · Cited by 451 · see citing works
Replication and Transcription of Mammalian Mitochondrial Dna
Fernández‐Silva, P., Enrı́quez, J. A., & Montoya, J. (2003) · Experimental Physiology · doi:10.1113/eph8802514 · Cited by 433 · see citing works
Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance
Ricquier, D., & Bouillaud, F. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00003.x · Cited by 385 · see citing works
Lee, G., Elwood, F., McNally, J., Weiszmann, J., Lindstrom, M., Amaral, K., Nakamura, M., Miao, S., Cao, P., Learned, R. M., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200743200 · Cited by 319 · see citing works
A Role for Brown Adipose Tissue in Diet‐Induced Thermogenesis
Rothwell, N. J., & Stock, M. J. (1997) · Obesity Research · doi:10.1002/j.1550-8528.1997.tb00591.x · Cited by 296 · see citing works
Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-α
Puigserver, P. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0802905 · Cited by 290 · see citing works
A Tissue-Specific Coactivator of Steroid Receptors, Identified in a Functional Genetic Screen
Knutti, D., Kaul, A., & Kralli, A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.7.2411-2422.2000 · Cited by 286 · see citing works
Sears, I. B., MacGinnitie, M. A., Kovács, L., & Graves, R. A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3410 · Cited by 270 · see citing works
Ziouzenkova, O., Perrey, S., Asatryan, L., Hwang, J., MacNaul, K. L., Moller, D. E., Rader, D. J., Sevanian, A., Zechner, R., Höefler, G., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0538015100 · Cited by 251 · see citing works
Muoio, D. M., Way, J. M., Tanner, C. J., Winegar, D. A., Kliewer, S. A., Houmard, J. A., Kraus, W. E., & Dohm, G. L. (2002) · Diabetes · doi:10.2337/diabetes.51.4.901 · Cited by 226 · see citing works
Ukropcova, B., McNeil, M., Sereda, O., de Jonge, L., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24332 · Cited by 213 · see citing works
Self-citationSemple, R. K., Crowley, V. C., Sewter, C. P., Laudes, M., Christodoulides, C., Considine, R. V., Vidal-Puig, A., & O'Rahilly, S. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802482 · Cited by 203 · see citing works
Halvorsen, Y. C., Bond, A., Sen, A., Franklin, D. M., Lea-Currie, Y. R., Sujkowski, D., Ellis, P. N., Wilkison, W. O., & Gimble, J. M. (2001) · Metabolism · doi:10.1053/meta.2001.21690 · Cited by 200 · see citing works
Self-citationBogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.7.1660 · Cited by 197 · see citing works
Self-citationPPARα is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue
Lee, Y., Yu, X., Gonzales, F., Mangelsdorf, D. J., Wang, M.-Y., Richardson, C., Witters, L. A., & Unger, R. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182420899 · Cited by 181 · see citing works
Effect of pioglitazone on body composition and energy expenditure: a randomized controlled trial
Smith, S. R., de Jonge, L., Volaufova, J., Li, Y., Xie, H., & Bray, G. A. (2005) · Metabolism · doi:10.1016/j.metabol.2004.07.008 · Cited by 176 · see citing works
Self-citationFukui, Y., Masui, S., Osada, S., Umesono, K., & Motojima, K. (2000) · Diabetes · doi:10.2337/diabetes.49.5.759 · Cited by 168 · see citing works
Digby, J. E., Montague, C. T., Sewter, C. P., Sanders, L., Wilkison, W. O., O'Rahilly, S., & Prins, J. B. (1998) · Diabetes · doi:10.2337/diab.47.1.138 · Cited by 134 · see citing works
Sell, H., Berger, J. P., Samson, P., Castriota, G. A., Lalonde, J., Deshaies, Y., & Richard, D. (2004) · Endocrinology · doi:10.1210/en.2004-0321 · Cited by 130 · see citing works
PGC-1 Functions as a Transcriptional Coactivator for the Retinoid X Receptors
Delerive, P., Wu, Y., Burris, T. P., Chin, W. W., & Suen, C. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109409200 · Cited by 108 · see citing works
Dulloo, A. G., Gubler, M., Montani, J.-P., Seydoux, J., & Solinas, G. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802861 · Cited by 87 · see citing works
Role of Leptin in Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Expression1
Kakuma, T., Wang, Z.-W., Pan, W., Unger, R. H., & Zhou, Y.-T. (2000) · Endocrinology · doi:10.1210/endo.141.12.7804 · Cited by 76 · see citing works
Wu, Y., Chin, W. W., Wang, Y., & Burris, T. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210910200 · Cited by 65 · see citing works
Marette, A., & Bukowiecki, L. J. (1991) · Biochemical Journal · doi:10.1042/bj2770119 · Cited by 55 · see citing works
Mitochondrial uncoupling proteins (UCPs) and obesity.
Rock, E., Winklhofer-Roob, B. M., Ribalta, J., Scotter, M., Vasson, M., Brtko, J., Brigelius‐Flohé, R., Bronner, A., & Azaı̈s-Braesco, V. (2001) · PubMed · Cited by 54 · see citing works
Mitochondrial uncoupling proteins in human physiology and disease.
Hagen, T., & Vidal‐Puig, A. (2002) · PubMed · Cited by 47 · see citing works
Comparison of adipose tissue changes following administration of rosiglitazone in the dog and rat
Toseland, C. D. N., Campbell, S., Francis, I., Bugelski, P. J., & Mehdi, N. (2001) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2001.00117.x · Cited by 43 · see citing works
Digby, J., Montague, C. T., Sewter, C. P., et al. (1998) · Diabetes · doi:10.2337/diabetes.47.1.138 · Cited by 23 · see citing works
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Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551 · see citing works
Developmental programming of obesity in mammals
Taylor, P. D., & Poston, L. (2007) · Experimental Physiology · doi:10.1113/expphysiol.2005.032854 · Cited by 473 · see citing works
Rong, J. X., Qiu, Y., Hansen, M. K., Zhu, L., Zhang, V., Xie, M., Okamoto, Y., Mattie, M. D., Higashiyama, H., Asano, S., et al. (2007) · Diabetes · doi:10.2337/db06-1135 · Cited by 335 · see citing works
Kaaman, M., Sparks, L. M., van Harmelen, V., Smith, S. R., Sjölin, E., Dahlman, I., & Arner, P. (2007) · Diabetologia · doi:10.1007/s00125-007-0818-6 · Cited by 217 · see citing works
Self-citationDiabetes regulates mitochondrial biogenesis and fission in mouse neurons
Edwards, J. L., Quattrini, A., Lentz, S. I., Figueroa-Romero, C., Cerri, F., Backus, C., Hong, Y., & Feldman, E. L. (2010) · Diabetologia · doi:10.1007/s00125-009-1553-y · Cited by 156 · see citing works
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Pagel-Langenickel, I., Bao, J., Pang, L., & Sack, M. N. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0003 · Cited by 154 · see citing works
Perrone, C. E., Mattocks, D. A. L., Jarvis-Morar, M., Plummer, J. D., & Orentreich, N. (2010) · Metabolism · doi:10.1016/j.metabol.2009.10.023 · Cited by 136 · see citing works
Mazzucotelli, A., Viguerie, N., Tiraby, C., Annicotte, J.-S., Mairal, A., Klimcakova, E., Lepin, E., Delmar, P., Dejean, S., Tavernier, G., et al. (2007) · Diabetes · doi:10.2337/db06-1465 · Cited by 90 · see citing works
Shi, X., Burkart, A., Nicoloro, S. M., Czech, M. P., Straubhaar, J., & Corvera, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800510200 · Cited by 70 · see citing works
Shen, W., Hao, J., Tian, C., Ren, J., Yang, L., Li, X., Luo, C., Cotma, C. W., & Liu, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002328 · Cited by 63 · see citing works
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- Authors
- Bogacka, I., Ukropcova, B., McNeil, M., Gimble, J. M., & Smith, S. R.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Bogacka, Iwona
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-12
- Volume
- 90
- Issue
- 12
- Pages
- 6650-6656
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1970246917
- Cited by
- 138
- References
- 45
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 3 · 2012: 11
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Takeda Pharmaceuticals North America
- Topics
- Health Sciences › Medicine › Physiology › 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 › Mitochondrial Function and Pathology
- Keywords
- mitochondrial biogenesis, white adipocytes, fatty acid oxidation, PPARγ agonists, PPARα agonist, forskolin, cAMP signaling, PGC-1α, TFAM, UCP1, carnitine palmitoyltransferase 1, medium-chain acyl-CoA dehydrogenase, mitochondrial DNA copy number, energy dissipation, preadipocyte differentiation, obesity, type 2 diabetes, insulin resistance
- MeSH terms
- Cells, Cultured, DNA, Mitochondrial, Fatty Acids, Colforsin, Glycerol, Humans, Mitochondria, Osmolar Concentration, Oxidation-Reduction, Gene Expression, Adipocytes, Gene Dosage, PPAR alpha, PPAR gamma
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