Abstract
AMP-activated protein kinase (AMPK) functions as a fuel sensor in the cell and is activated when cellular energy is depleted. Here we report that α-lipoic acid (α-LA), a cofactor of mitochondrial enzymes, decreases hypothalamic AMPK activity and causes profound weight loss in rodents by reducing food intake and enhancing energy expenditure. Activation of hypothalamic AMPK reverses the effects of α-LA on food intake and energy expenditure. Intracerebroventricular (i.c.v.) administration of glucose decreases hypothalamic AMPK activity, whereas inhibition of intracellular glucose utilization through the administration of 2-deoxyglucose increases hypothalamic AMPK activity and food intake. The 2-deoxyglucose-induced hyperphagia is reversed by inhibiting hypothalamic AMPK. Our findings indicate that hypothalamic AMPK is important in the central regulation of food intake and energy expenditure and that α-LA exerts anti-obesity effects by suppressing hypothalamic AMPK activity.
NOTE: In the version of this article initially published online, the name of an author was misspelled. The name of the twelfth author should be “Benoit Viollet”. This error has been corrected for the HTML and print versions of the article
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Change history
20 June 2004
Corrected the name to Benoit Viollet
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Acknowledgements
We thank M. Schwartz for critically reading the manuscript and E. Souil for technical support. This study was supported by a National Research Laboratory grant from the Ministry of Science and Technology (M1-0104-00-0103) and grants from the Ministry of Health & Welfare (03-PJ1-PG1-CH05-0005) of the Republic of Korea, the Korea Research Council of Fundamental Science and Technology, and the Asan Institute for Life Sciences (2004-006).
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The authors have submitted an application to the Korean patent office (no. 2000-31394), entitled “Agent increasing energy expenditure of the cell,” covering the use of α-lipoic acid as an anti-obesity agent.
Supplementary information
Supplementary Fig. 1
Anti-obesity effect of a-LA in genetically obese OLETF rats. (PDF 265 kb)
Supplementary Fig. 2
α-LA decreases fatty acid oxidation. (PDF 10 kb)
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Kim, MS., Park, JY., Namkoong, C. et al. Anti-obesity effects of α-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med 10, 727–733 (2004). https://doi.org/10.1038/nm1061
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DOI: https://doi.org/10.1038/nm1061
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