Editors' ChoiceMetabolism

The Fattened GOAT

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Science Signaling  21 Jul 2009:
Vol. 2, Issue 80, pp. ec245
DOI: 10.1126/scisignal.280ec245

The peptide hormone ghrelin, which is produced by the stomach and stimulates appetite and fat storage, must be acylated by ghrelin O-acyl transferase (GOAT) to incorporate medium-chain fatty acids (MCFAs) before it can bind to its receptor; des-acyl ghrelin is considered to be inactive. In humans receiving regular meals, concentrations of acylated ghrelin rise immediately before a meal and fall postprandially, a finding that has contributed to the proposal of ghrelin as a “hunger signal” that triggers food consumption during fasting. However, Kirchner et al. found that expression of the GOAT gene (Mboat4) was lower in mice that were fasted for a prolonged period than in mice fed ad libitum. In addition, over the fasting period, the concentrations of acyl ghrelin in the blood did not change, whereas those of des-acyl ghrelin decreased. Wild-type and Mboat4–/– mice were fed a diet containing medium-chain triglycerides (MCTs) based on octanoic (C8) and decanoic (C10) acids, which can be substrates for GOAT-mediated acylation of ghrelin. Mboat4–/– mice weighed less than wild-type mice, a finding that was attributed to decreased adiposity and not to lower food intake or to altered glucose homeostasis. In contrast, mice that overexpressed human GHRL and MBOAT4 genes in the liver gained more body weight and fat mass than wild-type mice when put on a diet containing a C8 MCT and lost this weight when returned to a normal chow diet. The authors suggest that GOAT and ghrelin are “lipid sensors” that link the availability of specific nutrients, such as easily digestible MCTs, with fat storage.

H. Kirchner, J. A. Gutierrez, P. J. Solenberg, P. T. Pfluger, T. A. Czyzyk, J. A. Willency, A. Schürmann, H.-G. Joost, R. J. Jandacek, J. E. Hale, M. L. Heiman, M. H. Tschöp, GOAT links dietary lipids with the endocrine control of energy balance. Nat. Med. 15, 741–745 (2009). [PubMed]

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