Impact of uremia on human adipose tissue phenotype.
BACKGROUND
Recognition of adipose-related signaling in surgery is increasing, although direct interrogation of human adipose has been sparse. Few scenarios rival uremia for health impact. We hypothesized that adipose from uremic patients holds a relatively higher adipose-derived hormone and proinflammatory adipokine signature; we simultaneously evaluated the impact of clinical parameters on adipose phenotype.


METHODS
Adipose was harvested from surgical patients. Histology and protein analyses were completed for select mediators.


RESULTS
In the overall cohort of 71 patients, the mean age was 63.4 y; 46.4% of patients had diabetes mellitus, 49.2% had hyperlipidemia, and 53.5% had coronary artery disease. Compared with nonuremic patients, uremic patients had one-tenth of the levels of leptin (P < 0.001), one-third of the levels of adiponectin (P < 0.001), and threefold higher levels of resistin (P < 0.001). Females had sixfold higher levels of leptin, 1.5-fold higher levels of adiponectin, and twofold higher levels of tumor necrosis factor alpha but equivalent resistin. There were differences in mediators when stratified by age. In both the obese and nonobese strata, we observed a concordant pattern of association (magnitude or significance) of uremia and leptin, adiponectin, and resistin. No differentials in other mediators emerged on body mass index stratification. Multiple regression analysis for leptin, adiponectin, and resistin (with age, gender, and uremia as independent variables) showed uremia as the highest independent predictor of all the three mediators.


CONCLUSIONS
Advanced chronic kidney disease is associated with perturbations in adipose-derived hormones (leptin, adiponectin, and resistin). Adipose adiponectin and leptin (in contrast to reported plasma levels) were lower in uremic patients; there is an inverse correlation between adipose resistin and renal function. Compared with other clinical parameters including body mass index, uremia dominates overall in determining adipose phenotype, highlighting the complex biological interplay between uremia and adipose biology.
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Karen J
KJ
Ho
Hui
H
Xue
Christine R
CR
Mauro
Binh
B
Nguyen
Peng
P
Yu
Ming
M
Tao
Michael A
MA
Seidman
Steven M
SM
Brunelli
Charles Keith
CK
Ozaki
D052242:Adiponectin / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D020738:Leptin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology; D052243:Resistin / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism / Q000503:physiopathology*; D014511:Uremia / Q000503:physiopathology*
D052242:Adiponectin; D020738:Leptin; D052243:Resistin