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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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.).
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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