Burning Stored Fat
Old drug may point the way to new treatments for diabetes and obesity
Published on Feb 10, 2013
ANN ARBOR—Researchers at the University of Michigan's Life Sciences Institute have found that amlexanox, an off-patent drug currently prescribed for the treatment of asthma and other uses, also reverses obesity, diabetes and fatty liver in mice. http://www.ns.umich.edu/new/releases/21179-old-drug-may-point-the-way-to-new-treatments-for-diabetes-and-obesity
An inhibitor of the protein kinases TBK1 and IKK-ε improves obesity-related metabolic dysfunctions in mice Shannon M Reilly1,9 , Shian-Huey Chiang1,8,9 , Stuart J Decker1 , Louise Chang1 , Maeran Uhm1–3 , Martha J Larsen1 , John R Rubin1 , Jonathan Mowers1–3 , Nicole M White1,8 , Irit Hochberg1,8 , Michael Downes4 , Ruth T Yu4 , Christopher Liddle4,5 , Ronald M Evans4,6 , Dayoung Oh7 , Pingping Li7 , Jerrold M Olefsky7 & Alan R Saltiel1–3 Emerging evidence suggests that inflammation provides a link between obesity and insulin resistance. The noncanonical IkB kinases IKK-« and TANK-binding kinase 1 (TBK1) are induced in liver and fat by NF-kB activation upon high-fat diet feeding and in turn initiate a program of counterinflammation that preserves energy storage. Here we report that amlexanox, an approved small-molecule therapeutic presently used in the clinic to treat aphthous ulcers and asthma, is an inhibitor of these kinases. Treatment of obese mice with amlexanox elevates energy expenditure through increased thermogenesis, producing weight loss, improved insulin sensitivity and decreased steatosis. Because of its record of safety in patients, amlexanox may be an interesting candidate for clinical evaluation in the treatment of obesity and related disorders.
Could this be how Amlexanox works? Orphanet J Rare Dis. 2012 Aug 31;7:58. Rescue of nonsense mutations by amlexanox in human cells. Gonzalez-Hilarion S, Beghyn T, Jia J, Debreuck N, Berte G, Mamchaoui K, Mouly V, Gruenert DC, Déprez B, Lejeune F. Université Lille Nord de France, IFR142, Lille, France. http://www.ncbi.nlm.nih.gov/pubmed/22938201 http://www.ojrd.com/content/7/1/58
ABSTRACT: BACKGROUND: Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence of nonsense mutations is often the absence of mutant gene expression due to the activation of an mRNA surveillance mechanism called nonsense-mediated mRNA decay (NMD). Strategies to rescue the expression of nonsense-containing mRNAs have been developed such as NMD inhibition or nonsense mutation readthrough. METHODS: Using a dedicated screening system, we sought molecules capable to block NMD. Additionally, 3 cell lines derived from patient cells and harboring a nonsense mutation were used to study the effect of the selected molecule on the level of nonsense-containing mRNAs and the synthesis of proteins from these mutant mRNAs. RESULTS: We demonstrate here that amlexanox, a drug used for decades, not only induces an increase in nonsense-containing mRNAs amount in treated cells, but also leads to the synthesis of the full-length protein in an efficient manner. We also demonstrated that these full length proteins are functional. CONCLUSIONS: As a result of this dual activity, amlexanox may be useful as a therapeutic approach for diseases caused by nonsense mutations.