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Cited by 355

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

Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects

Open access
Westerbacka, Jukka, Kolak, Maria, Kiviluoto, Tuula, Arkkila, Perttu, Sirén, Jukka, Hamsten, Anders, Fisher, Rachel M., Yki-Järvinen, Hannele·2007·Diabetes
DOI 10.2337/db07-0156
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Abstract

OBJECTIVE—The objective of this study is to quantitate expression of genes possibly contributing to insulin resistance and fat deposition in the human liver. RESEARCH DESIGN AND METHODS—A total of 24 subjects who had varying amounts of histologically determined fat in the liver ranging from normal (n = 8) to steatosis due to a nonalcoholic fatty liver (NAFL) (n = 16) were studied. The mRNA concentrations of 21 candidate genes associated with fatty acid metabolism, inflammation, and insulin sensitivity were quantitated in liver biopsies using real-time PCR. In addition, the subjects were characterized with respect to body composition and circulating markers of insulin sensitivity. RESULTS—The following genes were significantly upregulated in NAFL: peroxisome proliferator–activated receptor (PPAR)γ2 (2.8-fold), the monocyte-attracting chemokine CCL2 (monocyte chemoattractant protein [MCP]-1, 1.8-fold), and four genes associated with fatty acid metabolism (acyl-CoA synthetase long-chain family member 4 [ACSL4] [2.8-fold], fatty acid binding protein [FABP]4 [3.9-fold], FABP5 [2.5-fold], and lipoprotein lipase [LPL] [3.6-fold]). PPARγ coactivator 1 (PGC1) was significantly lower in subjects with NAFL than in those without. Genes significantly associated with obesity included nine genes: plasminogen activator inhibitor 1, PPARγ, PPARδ, MCP-1, CCL3 (macrophage inflammatory protein [MIP]-1α), PPARγ2, carnitine palmitoyltransferase (CPT1A), FABP4, and FABP5. The following parameters were associated with liver fat independent of obesity: serum adiponectin, insulin, C-peptide, and HDL cholesterol concentrations and the mRNA concentrations of MCP-1, MIP-1α, ACSL4, FABP4, FABP5, and LPL. CONCLUSIONS—Genes involved in fatty acid partitioning and binding, lipolysis, and monocyte/macrophage recruitment and inflammation are overexpressed in the human fatty liver.

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Metadata

Authors
Westerbacka, J., Kolak, M., Kiviluoto, T., Arkkila, P., Sirén, J., Hamsten, A., Fisher, R. M., & Yki-Järvinen, H.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2007-11-01
Volume
56
Issue
11
Pages
2759-2765
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db07-0156
OpenAlex
W2113063440
Cited by
355
References
48
FWCI
10.47
Type
journal article
Language
en
Open access
bronze

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