Abstract
Central nervous system nutrient sensing and afferent endocrine signaling have been established as parallel systems communicating metabolic status and energy availability in vertebrates. The only afferent endocrine signal known to require modification with a fatty acid side chain is the orexigenic hormone ghrelin. We find that the ghrelin O-acyl transferase (GOAT), which is essential for ghrelin acylation, is regulated by nutrient availability, depends on specific dietary lipids as acylation substrates and links ingested lipids to energy expenditure and body fat mass. These data implicate the ghrelin-GOAT system as a signaling pathway that alerts the central nervous system to the presence of dietary calories, rather than to their absence as is commonly accepted.
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Change history
04 September 2009
In the version of this article initially published, the fourth condition from the top in the key to the bar graphs in Figure 2c was mislabeled as ‘mC8’. The correct label is ‘hC8’. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We would like to thank J.E. Baker, B. Berger and J. Holland for their outstanding technical support. This manuscript was supported by the Leibniz Graduate College (H.K.) and by the US National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK069987 (to M.H.T.).
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H.K., P.T.P. and J.A.G. designed and performed most of the experiments and wrote the manuscript; P.J.S. generated mouse models; J.A.W. performed and interpreted mass spectrometry analyses; T.A.C. performed gene expression analyses; A.S., H.-G.J., R.J.J. and J.E.H. designed experiments, interpreted data and wrote the manuscript; and M.L.H. and M.H.T. conceptualized, analyzed and interpreted all studies and wrote the manuscript.
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J.A.G., P.J.S., T.A.C., J.A.W., J.E.H. and M.L.H. are employees and stock holders of the Eli Lilly Company.
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Kirchner, H., Gutierrez, J., Solenberg, P. et al. GOAT links dietary lipids with the endocrine control of energy balance. Nat Med 15, 741–745 (2009). https://doi.org/10.1038/nm.1997
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DOI: https://doi.org/10.1038/nm.1997
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