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Cited by 369Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

Impaired Preadipocyte Differentiation in Human Abdominal Obesity

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Isakson, Petter, Hammarstedt, Ann, Gustafson, Birgit, Smith, Ulf·2009·Diabetes
DOI 10.2337/db08-1770PMC PMC2699851
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Abstract

OBJECTIVE: We examined preadipocyte differentiation in obese and nonobese individuals and the effect of cytokines and wingless-type MMTV (mouse mammary tumor virus) integration site family, member 3A (Wnt3a) protein on preadipocyte differentiation and phenotype. RESEARCH DESIGN AND METHODS: Abdominal subcutaneous adipose tissue biopsies were obtained from a total of 51 donors with varying BMI. After isolation of the adipose and stromalvascular cells, inflammatory cells (CD14- and CD45-positive cells) were removed by immune magnetic separation. CD133-positive cells, containing early progenitor cells, were also isolated and quantified. The CD14- and CD45-negative preadipocytes were cultured with tumor necrosis factor (TNF)-α, interleukin (IL)-6, resistin, or Wnt3a with or without a differentiation cocktail. RESULTS: The number of preadipocytes able to differentiate to adipose cells was negatively correlated with both BMI and adipocyte cell size of the donors, whereas the number of CD133-positive cells was positively correlated with BMI, suggesting an impaired differentiation of preadipocytes in obesity. Cultured preadipocytes, like freshly isolated mature adipocytes, from obese individuals had an increased expression of mitogen-activated protein 4 kinase 4 (MAP4K4), which is known to inhibit peroxisome proliferator–activated receptor-γ induction. TNF-α, but not IL-6 or resistin, increased Wnt10b, completely inhibited the normal differentiation of the preadipocytes, and instead induced a proinflammatory and macrophage-like phenotype of the cells. CONCLUSIONS: The apparent number of preadipocytes in the abdominal subcutaneous tissue that can undergo differentiation is reduced in obesity with enlarged fat cells, possibly because of increased MAP4K4 levels. TNF-α promoted a macrophage-like phenotype of the preadipocytes, including several macrophage markers. These results document the plasticity of human preadipocytes and the inverse relationship between lipid storage and proinflammatory capacity.

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  • In a chronic inflammation microenvironment, preadipocytes can transdifferentiate into macrophage-like cells, with increased expression of pro-inflammatory cytokines and decreased adipogenic capacity in response to inflammatory stimuli.

    “In a chronic inflammation microenvironment, preadipocytes can transdifferentiate into macrophage‐like cells, with increased expression of pro‐inflammatory cytokines and decreased adipogenic capacity in response to inflammatory stimuli.[ 34 ]”

    From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [34]

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  1. [14]Gustafson B Hammarstedt A Andersson CX Smith U: Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol 2007; 27: 2276– 2283 17823366
  2. [22]Charriere G Cousin B Arnaud E Andre M Bacou F Penicaud L Casteilla L: Preadipocyte conversion to macrophage: evidence of plasticity. J Biol Chem 2003; 278: 9850– 9855 12519759
  3. [31]Di Gregorio GB Yao-Borengasser A Rasouli N Varma V Lu T Miles LM Ranganathan G Peterson CA McGehee RE Kern PA: Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes 2005; 54: 2305– 2313 16046295

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Authors
Isakson, P., Hammarstedt, A., Gustafson, B., & Smith, U.
Affiliations
University of Gothenburg (SE)
Corresponding author
Smith, Ulf
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2009-04-07
Volume
58
Issue
7
Pages
1550-1557
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db08-1770
PMC
PMC2699851
OpenAlex
W2149127304
Cited by
369
References
33
Citations by year
2026: 13 · 2025: 13 · 2024: 20 · 2023: 27 · 2022: 13 · 2021: 31 · 2020: 17 · 2019: 24 · 2018: 23 · 2017: 21 · 2016: 16 · 2015: 22 · 2014: 24 · 2013: 33 · 2012: 21
FWCI
15.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • European Commission
  • Stiftelsen för Strategisk Forskning
  • Novo Nordisk
  • Vetenskapsrådet
  • Novo Nordisk Fonden
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
preadipocyte differentiation, abdominal obesity, Wnt3a, Wnt10b, MAP4K4, TNF-α, interleukin-6, resistin, adipose tissue macrophages, adipocyte size, subcutaneous adipose tissue, PPARγ, adipose progenitor cells
MeSH terms
Abdomen, AC133 Antigen, Adult, Aged, Biopsy, Biopsy, Needle, Cell Differentiation, Enzyme-Linked Immunosorbent Assay, Glycoproteins, Humans, Inflammation, Middle Aged, Obesity, Peptides, Tumor Necrosis Factor-alpha, Antigens, CD, Body Mass Index, Polymerase Chain Reaction, Adipocytes, Cell Size, Bariatric Surgery, Wnt Proteins, Wnt3 Protein, Wnt3A Protein

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