title: Rapid improvement of hepatic steatosis after initiation of leptin substitution in a leptin-deficient girl.
abstract: BACKGROUND
  Leptin deficiency is associated with severe obesity and metabolic disturbances. Increased liver fat content has been reported in only one case beforehand, even though hepatic steatosis is a typical comorbidity of common obesity. It is also frequent in patients with lipodystrophy where it resolves under leptin therapy.
  
  
  METHODS
  In 2010, we reported a leptin-deficient patient with a novel homozygous mutation in the leptin gene and severe hepatic steatosis. We have now studied serum changes and changes in liver fat content during the substitution with recombinant methionyl human leptin.
  
  
  RESULTS
  After 23 weeks of leptin substitution, elevated transaminases, total cholesterol and low-density lipoprotein levels normalized. After 62 weeks, homeostasis model assessment of insulin resistance improved from 10.7 to 6.0 and body fat mass dropped from 50.2 to 37.8%. Liver fat content was drastically reduced from 49.7 to 9.4%. The first changes in liver fat content were detectable after 3 days of therapy.
  
  
  CONCLUSIONS
  Our patient showed a remarkable reduction of liver fat content during the treatment with recombinant methionyl human leptin. These changes occurred rapidly after initiation of the substitution, which implies that leptin has a direct effect on hepatic lipid metabolism in humans as it is seen in rodents.
authors: Division of Pediatric Endocrinology and Diabetes, University Medical Center Ulm, Ulm, Germany.
authors: J
authors: J
authors: von Schnurbein
authors: M
authors: M
authors: Heni
authors: A
authors: A
authors: Moss
authors: S A
authors: SA
authors: Nagel
authors: J
authors: J
authors: Machann
authors: H
authors: H
authors: Muehleder
authors: K M
authors: KM
authors: Debatin
authors: S
authors: S
authors: Farooqi
authors: M
authors: M
authors: Wabitsch
mesh_terms: D000293:Adolescent; D002784:Cholesterol / Q000097:blood; D005234:Fatty Liver / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006720:Homozygote; D020249:Hormone Replacement Therapy; D006801:Humans; D020738:Leptin / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D013997:Time Factors
chemical_list: D020738:Leptin; D008077:Lipoproteins, LDL; D002784:Cholesterol