title: Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients.
abstract: 11-β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to cortisol, mainly in the liver and visceral adipose tissue (VAT), and has been implicated in several metabolic disorders. The absence of systemic hypercortisolism in central obesity could be due to increased inactivation of cortisol to its tetrahydrometabolites by the hepatic enzymes 5α- and 5β-reductases. Our aim was to assess the expression of the reductases in the liver and of 11β-HSD1 in the liver and VAT in morbidly obese patients and to analyze their association with clinical, anthropometric, and biochemical parameters. Hepatic and VAT samples were obtained during bariatric surgery. 5α- and 5β-reductases, 11β-HSD1, and 18S expression was measured using real-time polymerase chain reaction. Anthropometric and biochemical variables were analyzed. Forty-one patients were recruited (age, 41.8 ± 10.6 years; body mass index, 42.1 ± 6.6 kg/m(2); 71% women). The expression of hepatic 5α- and 5β-reductases was positively correlated (r = +0.53, P = .004), and their expression levels were correlated with hepatic 11β-HSD1 expression (r = +0.61, P < .001 for 5α-reductase and r = +0.50, P < .001 for 5β-reductase). Hepatic 5α-reductase was associated with insulin (r = +0.34, P = .015). Visceral adipose tissue 11β-HSD1 expression was associated with glucose (r = +0.37, P = .025) and insulin (r = +0.54, P = .002). Our results showed that 5α-reductase and VAT 11β-HSD1 expressions were associated with insulinemia. These findings suggest that overexpression of 5α-reductase, through a higher inactivation of cortisol in the liver, could have a protective role in preserving hepatic sensitivity to insulin. The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11β-HSD1 to avoid systemic hypercortisolism.
authors.affiliation: Department of Endocrinology, School Of Medicine, Pontificia Universidad Católica De Chile, Santiago 8330074, Chile.
authors.forename: René
authors.initials: R
authors.lastname: Baudrand
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Domínguez
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Carvajal
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Riquelme
authors.forename: Carmen
authors.initials: C
authors.lastname: Campino
authors.forename: Stefano
authors.initials: S
authors.lastname: Macchiavello
authors.forename: Milan
authors.initials: M
authors.lastname: Bozinovic
authors.forename: Mauricio
authors.initials: M
authors.lastname: Morales
authors.forename: Margarita
authors.initials: M
authors.lastname: Pizarro
authors.forename: Nancy
authors.initials: N
authors.lastname: Solis
authors.forename: Alex
authors.initials: A
authors.lastname: Escalona
authors.forename: Camilo
authors.initials: C
authors.lastname: Boza
authors.forename: Marco
authors.initials: M
authors.lastname: Arrese
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Fardella
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D042944:Cholestenone 5 alpha-Reductase / Q000235:genetics / Q000378:metabolism*; D003480:Cushing Syndrome / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D012333:RNA, Messenger; D002097:C-Reactive Protein; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D042944:Cholestenone 5 alpha-Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006854:Hydrocortisone