Premium
Overexpression of 11β‐hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non‐alcoholic fatty liver disease
Author(s) -
Candia Roberto,
Riquelme Arnoldo,
Baudrand Rene,
Carvajal Cristian A.,
Morales Mauricio,
Solís Nancy,
Pizarro Margarita,
Escalona Alex,
Carrasco Gonzalo,
Boza Camilo,
Pérez Gustavo,
Padilla Oslando,
Cerda Jaime,
Fardella Carlos E.,
Arrese Marco
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02685.x
Subject(s) - 11β hydroxysteroid dehydrogenase type 1 , medicine , adipose tissue , endocrinology , fatty liver , corticosterone , dehydrogenase , hormone , disease , biology , enzyme , biochemistry
Abstract Background The enzyme 11β‐hydroxysteroid‐dehydrogenase type 1 (11β‐ HSD 1) catalyses the reactivation of intracellular cortisol. We explored the potential role of 11β‐ HSD 1 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‐ HSD 1 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‐ HSD 1 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. Conclusion Murine NAFLD is associated with portal hypercortisolism and11β‐ HSD 1 overexpression in VAT . In humans, 11β‐ HSD 1 VAT expression was associated with the presence of NAFLD . Thus, local corticosteroid production in VAT may contribute to NAFLD pathogenesis.