The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Rapid transformation of white adipocytes into fat-oxidizing machines
Open accessAbstract
Adenovirus-induced hyperleptinemia rapidly depletes body fat in normal rats without increasing free fatty acids and ketogenesis, implying that fat-storing adipocytes are oxidizing the fat. To analyze the ultrastructural changes of adipocytes accompanying this functional transformation, we examined the fat tissue by electron microscopy. After 14 days of hyperleptinemia, adipocytes had become shrunken, fatless, and encased in a thick basement-membrane-like matrix. They were crowded with mitochondria that were much smaller than those of brown adipocytes. Their gene expression profile revealed striking up-regulation of peroxisome proliferator-activated receptor γ coactivator 1α (an up-regulator of mitochondrial biogenesis not normally expressed in white fat), increased uncoupling proteins-1 and -2, and down-regulation of lipogenic enzymes. Phosphorylation of both acetyl CoA carboxylase and AMP-activated protein kinase was increased, thus explaining the increase in fatty acid oxidation. The ability to transform adipocytes into unique fat-burning cells may suggest novel therapeutic strategies for obesity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Zucker diabetic fatty rats transfected with leptin had a dramatic augmentation in PPAR␥ coactivator-1␣ expression in white adipose tissue with resultant delipidation (31).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [31]
In the citing paper
“Additionally, leptin upregulates mitochondria biogenesis through expression of PPAR␥ coactivator-1␣ (29,31).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [31]
In the citing paper
“Their shrunken adipocytes were filled with mitochondria, demonstrating conversion from fat-storing into fat-burning cells.”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [31]
In the citing paper
“Recent rodent studies suggest that this can be potentially overcome with a high enough dose, 22,24 a theory similar to insulin resistance.”
From Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy† (2005) · cites this paper as [24]
In the citing paper
“Higher mitochondrial density and even UCP1 can be induced in response to pharmacological or genetic alterations of white adipocytes (170 -177), suggesting that white adipose tissue could potentially be induced to acquire more oxidative metabolic phenotypes, promoting increased fuel consumption and thus energy expenditure.”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [173]
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 [173]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
How Matrix Metalloproteinases Regulate Cell Behavior
Sternlicht, M. D., & Werb, Z. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.463 · Cited by 3,959
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
Bustin, S. A. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0250169 · Cited by 3,844
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
Wang, Y.-X., Lee, C.-H., Tiep, S., Yu, R. T., Ham, J., Kang, H., & Evans, R. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00269-1 · Cited by 1,296
Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis
Lehman, J. J., Barger, P. M., Kovacs, A., Saffitz, J. E., Medeiros, D. M., & Kelly, D. P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10268 · Cited by 1,285
Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status
Hardie, D. G. (2003) · Endocrinology · doi:10.1210/en.2003-0982 · Cited by 994
A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.
McGarry, J. D., Mannaerts, G. P., & Foster, D. W. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108764 · Cited by 736
The Forkhead Transcription Factor Foxo1 Regulates Adipocyte Differentiation
Nakae, J., Kitamura, T., Kitamura, Y., Biggs, W., Arden, K. C., & Accili, D. (2003) · Developmental Cell · doi:10.1016/s1534-5807(02)00401-x · Cited by 729
Flagged first, then by citations
Research works printed but not linked: 3
- Cahill, G. F., Jr., Aoki, T. T. & Ruderman, N. B. (1973) Trans. Am. Clin. Climatol. Assn. 84, 184–202.
- Pierleoni, C., Verdenelli, F., Castellucci, M. & Cinti, S. (1998) Eur. J. Histochem. 42, 183–188.9857243
- 10.1210/jcem.87.5.8628 · DOI · Paper page
Cited by
Sorted by citations
Items 201–234 of 234
Fueling or Fighting Cancer? The Thermogenic Paradox of Brown Adipose Tissue
Guerrero, J. J. G., Encarnacion, P. C., Wang, C., del Rosario, M. A. S., Notarte, K. I., Zhou, J., Hsieh, Y.-T., Wang, W.-Y., Chang, C.-W., & Li, W.-C. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00699-3 · Cited by 2
Nitric Oxide and Cell Metabolism Dysfunction in the Metabolic Syndrome
Nisoli, E., & Moncada, S. (2005) · Elsevier eBooks · doi:10.1016/b978-84-8174-892-5.50018-8 · Cited by 1
Kulinsky, V. I., & Колесниченко, Л. С. (2007) · Biochemistry (Moscow) Supplement Series B Biomedical Chemistry · doi:10.1134/s1990750807020011 · Cited by 1
Ghrelin Regulation of AMPK in the Hypothalamus and Peripheral Tissues
Scerif, M., Kola, B., & Korbonits, M. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-903-7_5 · Cited by 1
AMPK and the Metabolic Syndrome
Viollet, B., & Andréelli, F. (2007) · Wiley eBooks · doi:10.1002/9783527621095.ch17 · Cited by 1
Noninvasive tracking of gene expression by reporter transgene imaging
Unger, R. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806875105 · Cited by 1
Self-citationLeptin: A Central Role in an Expanding Answer to Weight Loss
Holness, M. J. (2007) · Endocrinology · doi:10.1210/en.2007-1264 · Cited by 1
Lopes, A. B. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2014.tde-19112014-103920 · Cited by 1
Présentée DEVANT L'INSTITUT NATIONAL DES SCIENCES APPLIQUEES DE LYON
Docteur, L. G. D., & Zarrouki, B. (2007) · Cited by 1
Leptin Knockdown in Human Adipose Progenitor Cells Alters Adipocyte FunctionPreprint
Fuchs, L., Duc, D.-G. L., Bundalian, L., Hentschel, J., Richter, S., Kirstein, A., Engelberger, F., Grunewald, S., Meiler, J., Blüher, M., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5150934 · Cited by 1
Calcitriol and the Renin Angiotensin System, and Adipose Tissue Inflammation
Caserio, C. M. (2009)
T10c12 Conjugated Linoleic Acid Causes Delipidation in 3T3-L1 Adipocytes and Mice
Jiang, S. (2010) · Lincoln (University of Nebraska)
Anedda, A. (2010) · Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya)
Insulin sensitivity of hepatic glucose and lipid metabolism in animal models of hepatic steatosis
Grefhorst, A. (2006) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Hormone-Sensitive Lipase - New roles in adipose tissue biology
Ström, K. (2008) · Lund University Publications (Lund University)
Xie, L. (2008) · K-State Research Exchange (Kansas State University)
Pham, M. N. (2014) · UA Campus Repository (The University of Arizona)
Stäbler, A. (2009) · University writing server of the University of Hohenheim (Universität Hohenheim)
Molecular Mechanisms of Adipogenesis and Adipocyte Biology : Possible role of MKPs and STAMPs
Lindstad, T. (2010) · NORA - Norwegian Open Research Archives
A study on the mechanism of insulin resistance induction by abdominal obesity
Lee, S., 김동현, Kang, H., & 조진경 (2010) · Exercise Science · doi:10.15857/ksep.2010.19.1.27
Sutliff, R. L., Michael, C., Campbell, A. G., Kleinhenz, D. J., Olson, D. E., & JOSHUA, J. O. (2016)
Kinases and Mitochondrial Cycling
Carreras, M. C., & Poderoso, J. J. (2012) · Oxidative stress and disease · doi:10.1201/b12308-13
Convergence of leptin and insulin signaling networks in obesity
Sutherland, C. D., & Ashford, M. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511541643.006
Principles in Nitrosative Stress
Freye, E. C. K. (2011) · Springer eBooks · doi:10.1007/978-94-007-2036-7_6
Adipose Drug Targets for Obesity Treatment
Giacobino, J., Lehr, L., & Boss, O. (2007) · CRC Press eBooks · doi:10.1201/9781420005479.pt4
O impacto do tratamento de doxorrubicina nas funções do tecido adiposo branco.
Biondo, L. A. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2016.tde-11082016-152227
Cardiovascular and Metabolic Responses to Peripheral Leptin Infusion in Rats
Knight, W. D. (2008)
The role of leptin and insulin signaling in the hypothalamic control of liver metabolism
Faßhauer, M. (2013) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-4088
(2015) · Elsevier eBooks · doi:10.1016/b978-3-437-31618-0.16001-8
Neto, E. M. D. M. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2016.tde-16052017-135255
Yurchenko, O. V., Golubinskaya, D. D., & Korn, O. M. (2026) · Zoologischer Anzeiger · doi:10.1016/j.jcz.2026.05.003
FAM153A Is a Novel Biomarker of Human Thermogenic Adipocytes
Gyurina, K., Korpás, K. L., Bajusz-Rácz, A., Radványi, Á., Sasi-Szabó, L., Méhes, G., & Rőszer, T. (2026) · Cells · doi:10.3390/cells15151321
Regulation of macrophage inflammatory signaling pathways by AMP-activated protein kinase.
Zhu, Y. (2014) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/1649
Metadata
- Authors
- Orci, L., Cook, W. S., Ravazzola, M., Wang, M.-Y., Park, B.-H., Montesano, R., & Unger, R. H.
- Affiliations
- University of Geneva (CH)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-02-09
- Volume
- 101
- Issue
- 7
- Pages
- 2058-2063
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC357051
- OpenAlex
- W2011437165
- Cited by
- 234
- References
- 27
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 14 · 2013: 16 · 2012: 13
- FWCI
- 14.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- white adipocytes, fat oxidation, hyperleptinemia, adenovirus, mitochondrial biogenesis, PPARγ coactivator-1α, uncoupling proteins, AMPK, acetyl-CoA carboxylase, obesity treatment, adipocyte ultrastructure, basement membrane
- MeSH terms
- Adenoviridae, Adipose Tissue, Animals, Gene Expression Regulation, Hyperlipidemias, Mitochondria, Oxidation-Reduction, Rats, Zucker, RNA, Messenger, Transcription Factors, Biomarkers, Oxidants, Adipocytes, Leptin, Lipid Metabolism, Rats
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
