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Cited by 234Adipose Tissue and MetabolismPeroxisome Proliferator-Activated ReceptorsAdipokines, Inflammation, and Metabolic Diseases

Rapid transformation of white adipocytes into fat-oxidizing machines

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Orci, Lelio, Cook, William S., Ravazzola, Mariella, Wang, May-yun, Park, Byung-Hyun, Montesano, Roberto, Unger, Roger H.·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0308258100PMC PMC357051
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Abstract

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.

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Crossref · 10.1073/pnas.0308258100

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  • Zucker diabetic fatty rats transfected with leptin had a dramatic augmentation in PPARγ coactivator-1α expression in white adipose tissue with resultant delipidation.

    “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]

  • Leptin upregulates mitochondria biogenesis through expression of PPARγ coactivator-1α.

    “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]

  • Their shrunken adipocytes were filled with mitochondria, demonstrating conversion from fat-storing into fat-burning cells.

    “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]

  • Recent rodent studies suggest that leptin resistance can be potentially overcome with a high enough dose.

    “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]

  • Higher mitochondrial density and even UCP1 can be induced in response to pharmacological or genetic alterations of white adipocytes, suggesting that white adipose tissue could potentially be induced to acquire more oxidative metabolic phenotypes, promoting increased fuel consumption and thus energy expenditure.

    “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]

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Authors
Orci, L., Cook, W. S., Ravazzola, M., Wang, M.-Y., Park, B.-H., Montesano, R., & Unger, R. H.
Affiliations
University of Geneva (CH)
ORCID
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
DOI
10.1073/pnas.0308258100
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
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 › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Epidemiology › 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

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