Increased circulating leptin in alcoholic cirrhosis: Relation to release and disposal

Leptin is a cytokine peptide that decreases appetite and thereby food intak e and increases energy expenditure. It is produced in fat cells, but recent animal experiments have shown expression of leptin in modified stellate he patic cells. Because a change in circulating leptin in cirrhosis could be c aused by an altered production rate, altered disposal rate, or both, the pr esent study was undertaken to identify regions of leptin overflow into the blood stream and regions of leptin extraction. Patients with alcoholic cirr hosis (n = 16) and control patients without liver disease (n = 12) were stu died during catheterization with elective blood sampling from different vas cular beds. Blood samples for leptin determination (radioimmunoassay) were taken simultaneously from artery/hepatic vein, artery/renal vein, artery/il iac vein, and artery/cubital vein. Patients with cirrhosis had significantl y increased circulating leptin (7.3 vs. control 2.6 ng/mL, P < .002) that c orrelated directly to ascitic-free body mass index (r = 0.71, P < .005). A significant. renal extraction ratio of leptin was observed in control patie nts (0.16) and in patients with cirrhosis (0.07), but the latter value was significantly lower than in the control patients (-44%, P < .05) and invers ely correlated to serum creatinine (r = -0.60, P < .05). A significant, but equal, hepatosplanchnic extraction of leptin was observed in cirrhotic pat ients and control patients (0.08 vs. 0.07). In patients with cirrhosis a si gnificant cubital venous-arterial difference in leptin was observed, but no t in control patients. The iliac venous/arterial leptin ratio was significa ntly above 1.0 in both groups and of similar size (1.16 vs. 1.15), but a hi gher difference in concentration was found in the cirrhotic patients (+33%, P < .05). The spillover rates of leptin in cirrhotic patients may be even higher than estimated from the increased systemic veno-arterial gradients. In conclusion, the elevated circulating leptin in patients with cirrhosis i s most likely caused by a combination of decreased renal extraction and inc reased release from subcutaneous abdominal, femoral, gluteal, retroperitone al pelvic, and upper limb fat tissue areas. The hepatosplanchnic bed draine d through hepatic veins could not be identified as a source of increased ci rculating leptin in cirrhosis, but a contribution by the portosystemic coll ateral flow cannot be excluded.