Uraemic sera stimulate lipolysis in human adipocytes: role of perilipin

Background. Although chronic kidney disease (CKD) is associated with dyslipidaemia and insulin resistance, the exact cause(s) are unknown. Since adipose tissue plays an important role in the development of these complications, we investigated the effect of uraemic sera on human adipocytes in vitro. Methods. Cultured human adipocytes were incubated for 48 h with media containing sera from eight CKD Stage 5 patients or four (matched for age, sex and body mass index) healthy controls. Glycerol release (an index of lipolysis) was determined in conditioned media. RNA was isolated from the cells and quantitative polymerase chain reaction of genes involved in lipolysis was performed. In vivo lipolysis was determined by the plasma glycerol/total fat mass (from dual energy X-ray absorptiometry) ratio in 28 CKD patients and 28 matched controls. Results. Incubation with uraemic, but not control, sera resulted in a significant similar to 30% increase in spontaneous (basal) lipolysis (P <0.05). Furthermore, uraemic but not control sera induced a selective similar to 30% reduction of messenger RNA (mRNA) coding for the lipid-droplet-associated protein perilipin (PLIN) (P <0.05), while mRNA levels of lipases, adipokines and differentiation factors did not differ between the groups after incubation. Also, consistent with our in vitro data, in vivo plasma glycerol/fat mass ratio was significantly elevated in uraemic patients as compared to controls (5.23 +/- 4.1 versus 3.41 +/- 2.3 mu M/kg, P <0.05). Conclusions. Undefined circulating factors in CKD patients increase basal lipolysis in human adipocytes in vitro, probably by attenuating the expression of the lipolytic regulator PLIN. Since in vivo lipolysis is a well-established risk factor for insulin resistance and cardiovascular disease, these effects may promote increased morbidity and mortality in CKD.