11βHSD1 inhibition with AZD4017 improves lipid profiles and lean muscle mass in Idiopathic intracranial hypertension.

gnorimies20.15 shared this article with you from Inoreader 11βHSD1 inhibition with AZD4017 improves lipid profiles and lean muscle mass in Idiopathic intracranial hypertension. Via American Goiter Association 11βHSD1 inhibition with AZD4017 improves lipid profiles and lean muscle mass in Idiopathic intracranial hypertension. J Clin Endocrinol Metab. 2020 Oct 24;: Authors: Hardy RS, Botfield H, Markey K, Mitchell JL, Alimajstorovic Z, Westgate CSJ, Sagmeister M, Fairclough RJ, Ottridge RS, Yiangou A, H Storbeck KH, Taylor AE, Gilligan LC, Arlt W, Stewart PM, Tomlinson JW, Mollan SP, Lavery GG, Sinclair AJ Abstract BACKGROUND: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines pre-receptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension. METHODS: We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry (DXA). RESULTS: Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased HDL and cholesterol/HDL ratio), markers of hepatic function (decreased ALP and GGT) and increased lean muscle mass (1.8%, p<0.001). No changes in BMI, fat mass and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. CONCLUSIONS: These beneficial metabolic changes, represent a reduction in risk factors associated with raised intra-cranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia. PMID: 33098644 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.