title: Distinct roles of free leptin, bound leptin and soluble leptin receptor during the metabolic-inflammatory response in patients with liver cirrhosis.
abstract: BACKGROUND
  Alteration of the leptin system appears to play a role in the inflammatory-metabolic response in catabolic diseases such as chronic liver diseases.
  
  
  OBJECTIVE
  To investigate the association between leptin components, inflammatory markers and hepatic energy and substrate metabolism.
  
  
  METHODS
  We investigated in vivo hepatic substrate and leptin metabolism in 40 patients employing a combination of arterial and hepatic vein catheterization techniques and hepatic blood flow measurements. In addition to metabolic, inflammatory and neuroendocrine parameters, circulating levels of free leptin, bound leptin and soluble leptin receptor were determined.
  
  
  RESULTS
  Compared with controls, bound leptin and soluble leptin receptor levels were significantly elevated in cirrhosis, while free leptin did not increase. In cirrhosis bound leptin was correlated with soluble leptin receptor (r = 0.70, P < 0.001). Free leptin was positively correlated with metabolic parameters such as energy storage (body fat mass; r = 0.36, P < 0.05), insulin and insulin resistance (r = 0.48; r = 0.46, P < 0.01) as well as with hepatic glucose and energy release (r = 0.35 and r = 0.40, P < 0.05). In contrast, bound leptin and soluble leptin receptor were linked to proinflammatory cytokines and sympathetic activity (r = 0.61 and r = 0.56, P < 0.01).
  
  
  CONCLUSIONS
  The components of the leptin system (free leptin, bound leptin and soluble leptin receptor) have distinct roles in metabolic and inflammatory processes in patients with liver cirrhosis. The better understanding of this metabolic and inflammatory tissue-repair response may lead to innovative new therapeutic strategies in liver disease as well as in various other catabolic diseases.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany. johann.ockenga@charite.de
authors.forename: J
authors.initials: J
authors.lastname: Ockenga
authors.forename: U J F
authors.initials: UJ
authors.lastname: Tietge
authors.forename: K H W
authors.initials: KH
authors.lastname: Böker
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.forename: G
authors.initials: G
authors.lastname: Brabant
authors.forename: M J
authors.initials: MJ
authors.lastname: Bahr
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006505:Hepatitis / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000502:physiology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054411:Receptors, Leptin / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020738:Leptin; D054411:Receptors, Leptin