title: Des-acyl ghrelin analogs prevent high-fat-diet-induced dysregulation of glucose homeostasis.
abstract: There is clinical evidence that des-acyl ghrelin (DAG) favorably modulates glucose and lipid metabolism, although its mode of action is unknown. A murine model of prediabetes was used to assess possible mechanisms of action for DAG and a newly developed bioactive analog, AZP531. C57BL/6J mice were infused with saline, DAG, or AZP531 continuously for 4 wk, and fed either normal diet (ND) or normal diet for 2 wk followed by a high-fat diet (HFD) for 2 wk. Compared with mice in the ND group, HFD increased body and fat mass, caused glucose intolerance and insulin resistance, had proinflammatory effects in white adipose tissue, and caused lipid accumulation in brown adipose tissue. DAG and AZP531 treatment prevented HFD-induced proinflammatory effects, stimulated expression of mitochondrial function markers in brown adipose tissue, and prevented development of a prediabetic metabolic state. AZP531 also prevented a HFD-induced increase in acyl ghrelin levels. Our data indicate DAG analogs as potential treatment for the prevention of metabolic syndrome.
authors.affiliation: Dept. of Internal Medicine, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. p.delhanty@erasmusmc.nl
authors.forename: Patric J D
authors.initials: PJ
authors.lastname: Delhanty
authors.forename: Martin
authors.initials: M
authors.lastname: Huisman
authors.forename: Lucy Y
authors.initials: LY
authors.lastname: Baldeon-Rojas
authors.forename: Iris
authors.initials: I
authors.lastname: van den Berge
authors.forename: Aldo
authors.initials: A
authors.lastname: Grefhorst
authors.forename: Thierry
authors.initials: T
authors.lastname: Abribat
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van der Lely
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D054439:Ghrelin / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism / Q000517:prevention & control*; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology
chemical_list: D004041:Dietary Fats; D054439:Ghrelin; D007328:Insulin; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C581708:cyclic des-acyl ghrelin (6-13); C422650:ghrelin, des-n-octanoyl; D005947:Glucose