Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin.

Ghrelin, an acylated brain and gut peptide, is primarily produced by endocrine cells of the gastric mucosa for secretion into the circulation. The major active form of ghrelin is a 28-amino-acid peptide containing an n-octanoyl modification at serine that is essential for activity. Studies have identified multiple physiological functions for ghrelin, including GH release, appetite stimulation, and metabolic fuel preference. Until now, there has not been any report detailing the mechanism of ghrelin acyl modification. Here we report that ingestion of either medium-chain fatty acids (MCFAs) or medium-chain triacylglycerols (MCTs) increased the stomach concentrations of acylated ghrelin without changing the total (acyl- and des-acyl-) ghrelin amounts. After ingestion of either MCFAs or MCTs, the carbon chain lengths of the acyl groups attached to nascent ghrelin molecules corresponded to that of the ingested MCFAs or MCTs. Ghrelin peptides modified with n-butyryl or n-palmitoyl groups, however, could not be detected after ingestion of the corresponding short-chain or long-chain fatty acids, respectively. Moreover, n-heptanoyl ghrelin, an unnatural form of ghrelin, could be detected in the stomach of mice after ingestion of either n-heptanoic acid or glyceryl triheptanoate. These findings indicate that ingested medium-chain fatty acids are directly used for the acylation of ghrelin.

[1]  G. Yancopoulos,et al.  Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Tilghman,et al.  Glyceroneogenesis and the Triglyceride/Fatty Acid Cycle* , 2003, Journal of Biological Chemistry.

[3]  K. Hanada,et al.  Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. , 2003, Biochimica et biophysica acta.

[4]  K. Kangawa,et al.  Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure. , 2003, Current opinion in pharmacology.

[5]  T. Mizushima,et al.  Structural Divergence of Human Ghrelin , 2003, The Journal of Biological Chemistry.

[6]  V. Darras,et al.  Chicken ghrelin: purification, cDNA cloning, and biological activity. , 2002, Endocrinology.

[7]  H. Vaudry,et al.  Immunohistochemical localization and biochemical characterization of ghrelin in the brain and stomach of the frog Rana esculenta , 2002, The Journal of comparative neurology.

[8]  Márta Korbonits,et al.  The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. , 2002, The Journal of clinical endocrinology and metabolism.

[9]  Hideo Oya,et al.  Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel growth hormone-releasing peptide, in healthy humans. , 2002, Clinical science.

[10]  K. Kangawa,et al.  Bullfrog Ghrelin Is Modified by n-Octanoic Acid at Its Third Threonine Residue* , 2001, The Journal of Biological Chemistry.

[11]  R. Batterham,et al.  Ghrelin causes hyperphagia and obesity in rats. , 2001, Diabetes.

[12]  W. Shimizu,et al.  Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure , 2001, Circulation.

[13]  K. Kangawa,et al.  Structure-activity relationship of ghrelin: pharmacological study of ghrelin peptides. , 2001, Biochemical and biophysical research communications.

[14]  K. Hosoda,et al.  Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. , 2001, Diabetes.

[15]  F. Hegardt,et al.  Developmental changes in carnitine octanoyltransferase gene expression in intestine and liver of suckling rats. , 2001, Archives of biochemistry and biophysics.

[16]  M. Nakazato,et al.  A role for ghrelin in the central regulation of feeding , 2001, Nature.

[17]  K. Kangawa,et al.  Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. , 2000, Biochemical and biophysical research communications.

[18]  K. Hosoda,et al.  Kidney produces a novel acylated peptide, ghrelin , 2000, FEBS letters.

[19]  K. Nakao,et al.  Ghrelin strongly stimulates growth hormone release in humans. , 2000, The Journal of clinical endocrinology and metabolism.

[20]  F. Casanueva,et al.  Ghrelin-induced growth hormone secretion in humans. , 2000, European journal of endocrinology.

[21]  M. Nakazato,et al.  Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. , 2000, Endocrinology.

[22]  M. Tschöp,et al.  Ghrelin induces adiposity in rodents , 2000, Nature.

[23]  M. Papotti,et al.  Preliminary evidence that Ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans , 2000, Journal of endocrinological investigation.

[24]  K. Kangawa,et al.  Purification and Characterization of Rat des-Gln14-Ghrelin, a Second Endogenous Ligand for the Growth Hormone Secretagogue Receptor* , 2000, The Journal of Biological Chemistry.

[25]  M. Nakazato,et al.  Ghrelin is a growth-hormone-releasing acylated peptide from stomach , 1999, Nature.

[26]  S. Eaton,et al.  Mammalian mitochondrial beta-oxidation. , 1996, The Biochemical journal.

[27]  M. S. Murthy,et al.  Purification of the medium-chain/long-chain (COT/CPT) carnitine acyltransferase of rat liver microsomes. , 1992, Protein expression and purification.

[28]  F. Muskiet,et al.  Vitamin E, lipid fractions, and fatty acid composition of colostrum, transitional milk, and mature milk: an international comparative study. , 1991, The American journal of clinical nutrition.

[29]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[30]  S. Frost,et al.  Studies on fat digestion, absorption, and transport in the suckling rat. I. Fatty acid composition and concentrations of major lipid components. , 1981, Journal of lipid research.

[31]  R. Gibson,et al.  Fatty acid composition of human colostrum and mature breast milk. , 1981, The American journal of clinical nutrition.

[32]  H. E. Solberg.  Carnitine octanoyltransferase. Evidence for a new enzyme in mitochondria , 1971, FEBS letters.

[33]  N. Greenberger,et al.  Medium-chain triglycerides. , 1969, The New England journal of medicine.

[34]  G. Greeley,et al.  Printed in U.S.A. Copyright © 2002 by The Endocrine Society Ghrelin, A New Gastrointestinal Endocrine Peptide that Stimulates Insulin Secretion: Enteric Distribution, Ontogeny, Influence of Endocrine, and Dietary Manipulations , 2022 .

[35]  T. Arima,et al.  Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion , 2002 .

[36]  T. M. Lewin,et al.  Physiological and nutritional regulation of enzymes of triacylglycerol synthesis. , 2000, Annual review of nutrition.

[37]  M. Karas,et al.  Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. , 1990, Methods in enzymology.

[38]  V. Babayan.  Medium-chain triglycerides—their composition, preparation, and application , 1968, Journal of the American Oil Chemists' Society.