title: Overexpression of 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease.
abstract: BACKGROUND
  The enzyme 11β-hydroxysteroid-dehydrogenase type 1 (11β-HSD1) catalyses the reactivation of intracellular cortisol. We explored the potential role of 11β-HSD1 overexpression in visceral adipose tissue (VAT) in non-alcoholic fatty liver disease (NAFLD) assessing sequential changes of enzyme expression, in hepatic and adipose tissue, and the occurrence of portal hypercortisolism in obese mice. 11β-HSD1 expression was also assessed in tissues from obese patients undergoing bariatric surgery.
  
  
  METHODS
  Peripheral and portal corticosterone levels and liver histology were assessed in ob/ob mice at two time points (8-12 weeks of age). 11β-HSD1 tissue expression was assessed in by RT-pcr in ob/ob mice and in 49 morbidly obese patients.
  
  
  RESULTS
  Portal corticosterone serum levels were higher in obese mice with a 26% decrease between 8 and 12 weeks of age (controls: 78.3 ± 19.7 ng/ml, 8-week-old ob/ob: 167.5 ± 14.5 ng/ml and 12-week-old ob/ob: 124.3 ± 28 ng/ml, P < 0.05). No significant differences were found in peripheral corticosterone serum levels. Expression of 11β-HSD1 was lower in the liver [-45% at 8 weeks and -35% at 12-weeks (P = 0.0001)] and highly overexpressed in VAT in obese mice, compared to controls (128-fold higher in 8-week-old ob/ob and 41-fold higher in 12-week-old ob/ob, P < 0.01). No significant differences were seen in the expression of 11β-HSD1 in subcutaneous adipose tissue. In multivariate analysis, human 11β-HSD1 expression in VAT (OR: 1.385 ± 1.010-1.910) was associated with NAFLD.
  
  
  CONCLUSIONS
  Murine NAFLD is associated with portal hypercortisolism and11β-HSD1 overexpression in VAT. In humans, 11β-HSD1 VAT expression was associated with the presence of NAFLD. Thus, local corticosteroid production in VAT may contribute to NAFLD pathogenesis.
authors.affiliation: Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Candia
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Riquelme
authors.forename: Rene
authors.initials: R
authors.lastname: Baudrand
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Carvajal
authors.forename: Mauricio
authors.initials: M
authors.lastname: Morales
authors.forename: Nancy
authors.initials: N
authors.lastname: Solís
authors.forename: Margarita
authors.initials: M
authors.lastname: Pizarro
authors.forename: Alex
authors.initials: A
authors.lastname: Escalona
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Carrasco
authors.forename: Camilo
authors.initials: C
authors.lastname: Boza
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pérez
authors.forename: Oslando
authors.initials: O
authors.lastname: Padilla
authors.forename: Jaime
authors.initials: J
authors.lastname: Cerda
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Fardella
authors.forename: Marco
authors.initials: M
authors.lastname: Arrese
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D003480:Cushing Syndrome / Q000150:complications / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000150:complications* / Q000201:enzymology*; D020869:Gene Expression Profiling; D006801:Humans; D050152:Intra-Abdominal Fat / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000150:complications*; D016017:Odds Ratio; D012372:ROC Curve; D014280:Triglycerides / Q000097:blood
chemical_list: D017931:DNA Primers; D014280:Triglycerides; D002784:Cholesterol; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000410:Alanine Transaminase; D003345:Corticosterone