title: Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.
abstract: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB).
  
  
  
  We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1min-1) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp.
  
  
  
  Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion.
  
  
  
  These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Robyn A
authors.identifier: 0000-0002-6398-935X
authors.initials: RA
authors.lastname: Tamboli
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Joseph
authors.initials: J
authors.lastname: Antoun
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Reem M
authors.initials: RM
authors.lastname: Sidani
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Austin
authors.initials: A
authors.lastname: Clements
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Harmata
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Pam
authors.initials: P
authors.lastname: Marks-Shulman
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, Virginia.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gaylinn
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Brandon
authors.initials: B
authors.lastname: Williams
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Clements
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Vance L
authors.identifier: 0000-0002-5267-8951
authors.initials: VL
authors.lastname: Albaugh
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Naji N
authors.initials: NN
authors.lastname: Abumrad
mesh_terms: D000215:Acylation; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000009:adverse effects; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects; D015390:Gastric Bypass; D054439:Ghrelin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D005943:Gluconeogenesis / Q000187:drug effects; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000819:agonists* / Q000097:blood / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009767:Obesity, Morbid / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D010191:Pancreatic Polypeptide / Q000819:agonists / Q000097:blood / Q000378:metabolism; D050418:Pancreatic Polypeptide-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011182:Postoperative Care; D011300:Preoperative Care; D011498:Protein Precursors / Q000819:agonists / Q000097:blood / Q000378:metabolism; D016037:Single-Blind Method
chemical_list: D019440:Anti-Obesity Agents; C515349:GHRL protein, human; D054439:Ghrelin; C043710:PPY protein, human; D011498:Protein Precursors; D019382:Human Growth Hormone; D010191:Pancreatic Polypeptide
keywords: bariatric surgery; ghrelin; glucose metabolism; insulin resistance