-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice
نویسندگان
چکیده
Anne Hermanowski-Vosatka, James M. Balkovec, Kang Cheng, Howard Y. Chen, Melba Hernandez, Gloria C. Koo, Cheryl B. Le Grand, Zhihua Li, Joseph M. Metzger, Steven S. Mundt, Heather Noonan, Christian N. Nunes, Steven H. Olson, Bill Pikounis, Ning Ren, Nancy Robertson, James M. Schaeffer, Kashmira Shah, Martin S. Springer, Alison M. Strack, Matthias Strowski, Kenneth Wu, TsueiJu Wu, Jianying Xiao, Bei B. Zhang, Samuel D. Wright, and Rolf Thieringer
منابع مشابه
11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice
The enzyme 11beta-hydroxysteroid dehydrogenase (HSD) type 1 converts inactive cortisone into active cortisol in cells, thereby raising the effective glucocorticoid (GC) tone above serum levels. We report that pharmacologic inhibition of 11beta-HSD1 has a therapeutic effect in mouse models of metabolic syndrome. Administration of a selective, potent 11beta-HSD1 inhibitor lowered body weight, ins...
متن کامل11β-HSD1 inhibition reduces atherosclerosis in mice by altering proinflammatory gene expression in the vasculature.
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is implicated in the etiology of metabolic syndrome. We previously showed that pharmacological inhibition of 11β-HSD1 ameliorated multiple facets of metabolic syndrome and attenuated atherosclerosis in ApoE-/- mice. However, the molecular mechanism underlying the atheroprotective effect was not clear. In this study, we tested whether and how 11...
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Glucocorticoids, which are well established to regulate body fat mass distribution, adipocyte lipolysis, hepatic gluconeogenesis, and hepatocyte VLDL secretion, are speculated to play a role in the pathology of metabolic syndrome. Recent focus has been on the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which is capable of regenerating, and thus amplifying, glucocortico...
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11β-Hydroxysteroid dehydrogenase type-1 (11β-HSD1) converts inert cortisone into active cortisol, amplifying intracellular glucocorticoid action. 11β-HSD1 deficiency improves cardiovascular risk factors in obesity but exacerbates acute inflammation. To determine the effects of 11β-HSD1 deficiency on atherosclerosis and its inflammation, atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) ...
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BACKGROUND Stearoyl-CoA desaturase 1 (SCD1) is a critical regulator of energy metabolism and inflammation. We have previously reported that inhibition of SCD1 in hyperlipidemic mice fed a saturated fatty acid (SFA)-enriched diet prevented development of the metabolic syndrome, yet surprisingly promoted severe atherosclerosis. In this study we tested whether dietary fish oil supplementation coul...
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