Reductions in plasma cholesterol levels after fenofibrate treatment are negatively correlated with resistin expression in human adipose tissue.

The adipocyte-derived cytokine, resistin, has been proposed as the link between obesity and type 2 diabetes mellitus in murine models. In humans, resistin is identical to FIZZ3 (found in inflammatory zone 3), which belongs to a family of proteins that appears to be involved in inflammatory processes. To study the mechanisms by which fibrates improve glucose homeostasis, we determined resistin mRNA levels by using relative quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) in omental white adipose tissue samples obtained from patients treated with placebo or fenofibrate (200 mg/d) for 8 weeks before elective cholecystectomy. Fenofibrate treatment reduced total plasma cholesterol and low-density lipoprotein (LDL)-cholesterol levels by 24% and 35%, respectively. Compared with placebo values, a 2.4-fold induction in resistin mRNA levels was observed in white adipose tissue of fenofibrate-treated patients, whereas no changes were observed in the mRNA levels of the well-known perosixome proliferator-activated receptor (PPAR) target genes CD36, acyl-CoA oxidase, and carnitine palmitoyltransferase. These findings indicate that resistin changes were not related to PPAR activation by fenofibrate. Interestingly, resistin mRNA levels showed a negative correlation with plasma cholesterol levels (r2 =.53, P =.039, n = 8), but not with triglyceride levels (r2 =.02, P =.73, n = 8). These results suggest that cholesterol regulates resistin expression in human white adipose tissue.