Disulfiram Treatment Normalizes Body Weight in Obese Mice
- 주제(기타) Cell Biology
- 주제(기타) Endocrinology & Metabolism
- 설명문(일반) [Bernier, Michel; Mitchell, Sarah J.; Wahl, Devin; Ali, Ahmed; Kaiser, Tamzin; Aon, Miguel A.; Kim, Eun-Young; Petr, Michael A.; Di Germanio, Clara; Di Francesco, Andrea; Guiterrez, Vince; Enamorado, Ignacio Navas; de Cabo, Rafael] NIA, Expt Gerontol Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA; [Wahl, Devin; Harney, Dylan; Koay, Yen Chin; Pulpitel, Tamara; O'Sullivan, John; Larance, Mark; LeCouteur, David G.; Cogger, Victoria C.] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia; [Diaz, Antonio; Cuervo, Ana Maria] Albert Einstein Coll Med, Inst Aging Studies, Dept Dev & Mol Biol, Bronx, NY 10461 USA; [Singh, Abhishek; Price, Nathan L.; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Dept Pathol,Dept Comparat Med, Vasc Biol & Therapeut Program,Integrat Cell Signa, New Haven, CT 06510 USA; [Seo, Wonhyo; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA; [Wang, Mingy; Aon, Miguel A.; Wang, Yushi; Zhang, Jing; Zhang, Li; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA; [Kim, Eun-Young] KRIBB, Funct Genom Res Ctr, Daejeon 305806, South Korea; [Cai, Huan; Fishbein, Ken; Spencer, Richard G.; Egan, Josephine M.] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA; [Wahl, Devin; Warren, Alessa; Pulpitel, Tamara; LeCouteur, David G.; Cogger, Victoria C.] Sydney Med Sch, Concord Clin Sch, ANZAC Res Inst, Ageing & Alzheimers Inst, Concord, NSW 2139, Australia; [Koay, Yen Chin; O'Sullivan, John] Univ Sydney, Heart Res Inst, Sydney, NSW 2042, Australia; [Mach, John] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2065, Australia; [Mach, John] Univ Sydney, Sydney Med Sch, Sydney, NSW 2065, Australia; [Becker, Kevin G.] NIA, Lab Genet, Intramural Res Program, NIH, Baltimore, MD 21224 USA
- 등재 SCIE, SCOPUS
- 발행기관 CELL PRESS
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000182499
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.cmet.2020.04.019
초록/요약
Obesity is a top public health concern, and a molecule that safely treats obesity is urgently needed. Disulfiram (known commercially as Antabuse), an FDA-approved treatment for chronic alcohol addiction, exhibits anti-inflammatory properties and helps protect against certain types of cancer. Here, we show that in mice disul-firam treatment prevented body weight gain and abrogated the adverse impact of an obesogenic diet on in-sulin responsiveness while mitigating liver steatosis and pancreatic islet hypertrophy. Additionally, disulfiram treatment reversed established diet-induced obesity and metabolic dysfunctions in middle-aged mice. Re-ductions in feeding efficiency and increases in energy expenditure were associated with body weight regu-lation in response to long-term disulfiram treatment. Loss of fat tissue and an increase in liver fenestrations were also observed in rats on disulfiram. Given the potent anti-obesogenic effects in rodents, repurposing disulfiram in the clinic could represent a new strategy to treat obesity and its metabolic comorbidities.
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