Increased expression of the macrophage markers and of 11beta-HSD-1 in subcutaneous adipose tissue, but not in cultured monocyte-derived macrophages, is associated with liver fat in human obesity.
OBJECTIVE
To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-alpha), HSD11B1 (gene encoding 11beta-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects.


METHODS
Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity.


METHODS
Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2+/-1.0 kg/m(2)) and 10 healthy obese/overweight (33.1+/-1.7 kg/m(2)) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1+/-0.7 kg/m(2)) and seven healthy obese/overweight (36.9+/-2.2 kg/m(2)) women.


METHODS
Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR.


RESULTS
In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects.


CONCLUSIONS
Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.
Makkonen
J
J
Division of Diabetes, Department of Medicine, University of Helsinki and Minerva Medical Research Institute, FIN-00029 HUCH, Helsinki, Finland.
Westerbacka
J
J
Kolak
M
M
Sutinen
J
J
Cornér
A
A
Hamsten
A
A
Fisher
R M
RM
Yki-Järvinen
H
H
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000273:Adipose Tissue / Q000033:anatomy & histology; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D005215:Fasting; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000033:anatomy & histology*; D008264:Macrophages / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism*; D000097382:CD68 Molecule
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D039481:CD11b Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C509295:ITGAM protein, human