Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1...good for lipodystrophy?

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Diabetologia. 2004 Oct;47(10):1668-71. Epub 2004 Sep 29.In the lipodystrophy associated with highly active antiretroviral therapy, pseudo-Cushing's syndrome is associated with increased regeneration of cortisol by 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue.Sutinen J, Kannisto K, Korsheninnikova E, Nyman T, Ehrenborg E, R, Wake DJ, Hamsten A, BR, Yki-Järvinen H.Division of Diabetes, Department of Medicine, University of Helsinki, Helsinki, Finland. jussi.sutinen@...AbstractAIMS/HYPOTHESIS: Highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV) is associated with a poorly understood lipodystrophic and hypertriglyceridaemic syndrome, which resembles Cushing's syndrome, but in which plasma cortisol is not elevated. We tested the hypothesis that this HAART-associated lipodystrophy is explained by increased local regeneration of cortisol from inactive cortisone within

adipose tissue, catalysed by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1).METHODS: In this cross-sectional study, a previously described cohort of 30 HIV-infected patients with lipodystrophy were compared with 13 HIV-infected patients without lipodystrophy. Intra-abdominal and subcutaneous adipose tissue were quantified using magnetic resonance imaging. Gene expression in subcutaneous fat was measured using real-time PCR. Urine cortisol and its metabolites were analysed by gas chromatography/mass spectrometry.RESULTS: Patients with lipodystrophy had significantly higher 11beta-HSD1 mRNA concentrations (relative to beta2-microglobulin mRNA) in subcutaneous adipose tissue than non-lipodystrophic patients (0.29+/-0.20 vs 0.09+/-0.07, p=0.0004) and higher ratios of urinary cortisol : cortisone metabolites. Adipose tissue 11beta-HSD1 mRNA correlated with multiple features of insulin resistance and with mRNA concentrations for glucocorticoid receptor and angiotensinogen.CONCLUSIONS/INTERPRETATION: In adipose tissue of patients with HAART-associated lipodystrophy, 11beta-HSD1 mRNA is increased and its concentration is correlated with features of insulin resistance. We suggest that increased adipose tissue 11beta-HSD1 may explain the pseudo-Cushing's features in patients with HAART-associated lipodystrophy, and is a potential therapeutic target.PMID: 15455200 [PubMed - indexed for MEDLINE]More on the enzyme 11beta-hydroxysteroid: http://qualitycounts.com/fp11beta-HSD1.htmThis is the supplement that may work for lipodystrophy ( we need dat) : http://www.ncbi.nlm.nih.gov/pubmed/20718744?dopt=Abstract Regards, VergelPoWeRUSA.org