title: In vivo degradation of cholesterol to bile acids is reduced in patients receiving parenteral nutrition.
abstract: BACKGROUND
  Artificial nutrition is frequently associated with hepatobiliary complications, probably due to the inherent derangement of the gastrointestinal tract physiology. Alterations of hepatic lipid metabolism are likely to be involved. The aim of the present study was to investigate the effect of artificial nutrition on bile acid production, a key event in cholesterol homeostasis, in humans.
  
  
  METHODS
  Eleven patients receiving artificial nutrition, either parenteral nutrition (PN; n = 6) or enteral nutrition (EN; n = 5) with no previous history of liver disease, underwent analysis of cholesterol 7α-hydroxylation rates in vivo, a measure of bile acid formation, by isotope release analysis after intravenous injection of [7α-(3)H]cholesterol. The results were compared with those obtained in a population of 16 age-matched control subjects.
  
  
  RESULTS
  Hydroxylation rates were lower in patients with artificial nutrition (PN: 94 ± 13 mg/d; EN: 230 ± 39 mg/d, mean ± SEM) when compared with controls (385 ± 47 mg/d) (P < .01, 1-way analysis of variance). In a patient receiving EN, hydroxylation rates increased 3.5-fold after treatment with the cholecystokinin analogue ceruletide (20 µg bid for 2 weeks intramuscularly). Serum lathosterol-to-cholesterol ratio, a marker of cholesterol synthesis, was also significantly reduced in artificial nutrition, whereas serum levels of fibroblast growth factor 19 (FGF19) were increased.
  
  
  CONCLUSIONS
  In vivo 7α-hydroxylation is suppressed in artificial nutrition, particularly in PN. The finding associates with reduced cholesterol production, possibly as a metabolic consequence. The data suggest a regulatory role of gastrointestinal hormones and FGF19 on bile acid production and might suggest a pathophysiological basis for some common complications of artificial nutrition, such as gallstone disease and cholestasis.
authors: Dipartimento di Medicina, Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.
authors: Lucia
authors: L
authors: Carulli
authors: Marina
authors: M
authors: Del Puppo
authors: Claudia
authors: C
authors: Anzivino
authors: Lisa
authors: L
authors: Zambianchi
authors: Chiara
authors: C
authors: Gabbi
authors: Enrica
authors: E
authors: Baldelli
authors: Maria Rosaria
authors: MR
authors: Odoardi
authors: Paola
authors: P
authors: Loria
authors: Nicola
authors: N
authors: Carulli
authors: Marco
authors: M
authors: Bertolotti
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood*; D015992:Body Mass Index; D001835:Body Weight; D002766:Cholecystokinin / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood*; D004750:Enteral Nutrition / Q000009:adverse effects; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D005768:Gastrointestinal Hormones / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006900:Hydroxylation; D016014:Linear Models; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010288:Parenteral Nutrition / Q000009:adverse effects
chemical_list: D001647:Bile Acids and Salts; C117476:FGF19 protein, human; D005768:Gastrointestinal Hormones; D005346:Fibroblast Growth Factors; C001521:lathosterol; D002766:Cholecystokinin; D002784:Cholesterol
keywords: FGF19; artificial nutrition; bile acid synthesis; cholesterol homeostasis; lathosterol