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Cited by 317

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Adipose Tissue Inflammation and Increased Ceramide Content Characterize Subjects With High Liver Fat Content Independent of Obesity

Open access
Kolak, Maria, Westerbacka, Jukka, Velagapudi, Vidya R., Wågsäter, Dick, Yetukuri, Laxman, Makkonen, Janne, Rissanen, Aila, Häkkinen, Anna-Maija, Lindell, Monica, Bergholm, Robert, Hamsten, Anders, Eriksson, Per, Fisher, Rachel M., Orešic̆, Matej, Yki-Järvinen, Hannele·2007·Diabetes
DOI 10.2337/db07-0111
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Abstract

OBJECTIVE— We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity. RESEARCH DESIGN AND METHODS— A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 ± 0.3 vs. 14.4 ± 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations. RESULTS— Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator–activated receptor-γ and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group. CONCLUSIONS— Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.

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Metadata

Authors
Kolak, M., Westerbacka, J., Velagapudi, V. R., Wågsäter, D., Yetukuri, L., Makkonen, J., Rissanen, A., Häkkinen, A.-M., Lindell, M., Bergholm, R., Hamsten, A., Eriksson, P., Fisher, R. M., Orešic̆, M., & Yki-Järvinen, H.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2007-08-01
Volume
56
Issue
8
Pages
1960-1968
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db07-0111
OpenAlex
W2144331646
Cited by
317
References
48
FWCI
15.49
Type
journal article
Language
en
Open access
bronze

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