title: The gut hormone ghrelin partially reverses energy substrate metabolic alterations in the failing heart.
abstract: BACKGROUND
  The gut-derived hormone ghrelin, especially its acylated form, plays a major role in the regulation of systemic metabolism and exerts also relevant cardioprotective effects; hence, it has been proposed for the treatment of heart failure (HF). We tested the hypothesis that ghrelin can directly modulate cardiac energy substrate metabolism.
  
  
  RESULTS
  We used chronically instrumented dogs, 8 with pacing-induced HF and 6 normal controls. Human des-acyl ghrelin [1.2 nmol/kg per hour] was infused intravenously for 15 minutes, followed by washout (rebaseline) and infusion of acyl ghrelin at the same dose. (3)H-oleate and (14)C-glucose were coinfused and arterial and coronary sinus blood sampled to measure cardiac free fatty acid and glucose oxidation and lactate uptake. As expected, cardiac substrate metabolism was profoundly altered in HF because baseline oxidation levels of free fatty acids and glucose were, respectively, >70% lower and >160% higher compared with control. Neither des-acyl ghrelin nor acyl ghrelin significantly affected function and metabolism in normal hearts. However, in HF, des-acyl and acyl ghrelin enhanced myocardial oxygen consumption by 10.2±3.5% and 9.9±3.7%, respectively (P<0.05), and cardiac mechanical efficiency was not significantly altered. This was associated, respectively, with a 41.3±6.7% and 32.5±10.9% increase in free fatty acid oxidation and a 31.3±9.2% and 41.4±8.9% decrease in glucose oxidation (all P<0.05).
  
  
  CONCLUSIONS
  Acute increases in des-acyl or acyl ghrelin do not interfere with cardiac metabolism in normal dogs, whereas they enhance free fatty acid oxidation and reduce glucose oxidation in HF dogs, thus partially correcting metabolic alterations in HF. This novel mechanism might contribute to the cardioprotective effects of ghrelin in HF.
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Mitacchione
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Powers
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Gino
authors.initials: G
authors.lastname: Grifoni
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Felix
authors.initials: F
authors.lastname: Woitek
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Amy
authors.initials: A
authors.lastname: Lam
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Lien
authors.initials: L
authors.lastname: Ly
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Fabio
authors.initials: F
authors.lastname: Settanni
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Makarewich
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Ryan
authors.initials: R
authors.lastname: McCormick
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Letizia
authors.initials: L
authors.lastname: Trovato
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.).
authors.forename: Riccarda
authors.initials: R
authors.lastname: Granata
authors.affiliation: From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA (G.M., J.C.P., G.G., F.W., A.L., L.L., C.A.M., R.M., S.R.H., F.A.R.); Department of Medical Sciences, University of Turin, Turin, Italy (F.S., L.T., R.G.); and Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy (F.A.R.). fabio.recchia@temple.edu.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004285:Dogs; D004734:Energy Metabolism / Q000235:genetics*; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D054440:Receptors, Ghrelin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D054440:Receptors, Ghrelin; D012313:RNA
keywords: energy metabolism; hormones