Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity

被引:256
作者
Kolak, Maria
Westerbacka, Jukka
Velagapudi, Vidya R.
Wagsater, Dick
Yetukuri, Laxman
Makkonen, Janne
Rissanen, Aila
Hakkinen, Anna-Maija
Lindell, Monica
Bergholm, Robert
Hamsten, Anders
Eriksson, Per
Fisher, Rachel M.
Oresic, Matej
Yki-Jarvinen, Hannele
机构
[1] Karolinska Inst, King Gustaf V Res Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden
[2] Univ Helsinki, Dept Med, Div Diabet, Helsinki, Finland
[3] VTT Tech Res Ctr Finland, Espoo, Finland
[4] Minerva Med Res Inst, Helsinki, Finland
[5] Univ Helsinki, Obes Res Unit, Helsinki, Finland
[6] Univ Helsinki, Dept Oncol, Helsinki, Finland
关键词
D O I
10.2337/db07-0111
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-la, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator-activated receptor-gamma and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-Eke 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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页码:1960 / 1968
页数:9
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