Increased expression of pro-inflammatory genes in abdominal subcutaneous fat in advanced chronic kidney disease patients.
OBJECTIVE
Low-grade systemic inflammation, oxidative stress and peripheral insulin resistance are intimately associated and contribute to the increased risk of cardiovascular complications in advanced chronic kidney disease (CKD). Because altered adipose tissue activities have previously been linked to pathophysiological processes in various inflammatory and metabolic diseases we hypothesized that the uraemic milieu in patients with CKD may interact with the adipose tissue, provoking an unfavourable shift in its transcriptional output.


METHODS
Twenty-one adipokine mRNAs were quantified in abdominal subcutaneous adipose tissue (SAT) biopsies and serum/plasma concentrations of inflammatory markers and related protein products were measured.


METHODS
The study was conducted at the Karolinska University Hospital, Huddinge, and Karolinska Institutet, Stockholm, Sweden.


METHODS
Thirty-seven patients with CKD [15 women, median 58 (interquartile range 49-65) years] and nine nonuraemic individuals [four women, age 62 (45-64) years] were recruited prior to initiation of peritoneal dialysis catheter insertion or elective hernia repair/laparoscopic cholecystectomy, respectively.


RESULTS
Even after correction for body mass index, SAT from patients showed a significant upregulation of inflammatory pathway genes interleukin 6 (3.0-fold, P=0.0002) and suppressor of cytokine signalling 3 (2.5-fold, P=0.01), as well as downregulation of leptin (2.0-fold, P=0.03) and the oxidative stress genes uncoupling protein 2 (1.5-fold, P=0.03) and cytochrome b-245, alpha polypeptide (1.5-fold, P=0.005), in relation to controls.


CONCLUSIONS
These gene expression differences suggest that inflammatory and oxidative stress activities may be important features of the intrinsic properties of uraemic adipose tissue, which may have significant effects on the uraemic phenotype.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Centre for Molecular Medicine, L8:00 Karolinska University Hospital, 17176 Stockholm, Sweden. anna.witasp@ki.se
A
A
Witasp
J J
JJ
Carrero
O
O
Heimbürger
B
B
Lindholm
F
F
Hammarqvist
P
P
Stenvinkel
L
L
Nordfors
D054392:Adipokines / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D050151:Subcutaneous Fat / Q000378:metabolism*
D054392:Adipokines; D018836:Inflammation Mediators; D012333:RNA, Messenger