TY - JOUR
T1 - Des-acyl ghrelin analogs prevent high-fat-diet-induced dysregulation of glucose homeostasis
AU - Delhanty, Patric J.D.
AU - Huisman, Martin
AU - Baldeon-Rojas, Lucy Y.
AU - Van Den Berge, Iris
AU - Grefhorst, Aldo
AU - Abribat, Thierry
AU - Leenen, Pieter J.M.
AU - Themmen, Axel P.N.
AU - Van Der Lely, Aart Jan
PY - 2013/4
Y1 - 2013/4
N2 - 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 HFDinduced increase in acyl ghrelin levels. Our data indicate DAG analogs as potential treatment for the prevention of metabolic syndrome.
AB - 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 HFDinduced increase in acyl ghrelin levels. Our data indicate DAG analogs as potential treatment for the prevention of metabolic syndrome.
KW - Inflammation
KW - Insulin resistance
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=84875746147&partnerID=8YFLogxK
U2 - https://doi.org/10.1096/fj.12-221143
DO - https://doi.org/10.1096/fj.12-221143
M3 - Article
C2 - 23299855
SN - 0892-6638
VL - 27
SP - 1690
EP - 1700
JO - FASEB Journal
JF - FASEB Journal
IS - 4
ER -