Sub-chronic administration of stable GIP analog in mice decreases serum LPL activity and body weight

Ewa Szalowska*, Kees Meijer, Niels Kloosterhuis, Farhad Razaee, Marion Priebe, Roel J. Vonk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

Abstract

GIP receptor knockout mice were shown to be protected from the development of obesity on a high fat diet, suggesting a role of GIP in the development of obesity. In our study we aimed to test the hypothesis if excess of GIP could accelerate development of obesity and to identify GIP gene targets in adipose tissue. Therefore, mice were kept on a chow or a high fat diet and during the last 2 weeks D-Ala(2)-GIP or PBS injections were performed. Afterwards, serum LPL activity and several biochemical parameters (TG, FFA, cholesterol, glucose, insulin, resistin, IL-6, IL-1 beta, TNF alpha, GIP) were measured. Fat tissue was isolated and QPCR was performed for a set of genes involved in energy metabolism and inflammation. A DNA-microarray was used to identify GIP gene targets in adipose tissue of the chow diet group. We found that the D-Ala(2)-GIP injections caused a significant decrease in both body weight and LPL activity compared to controls. Serum biochemical parameters were not affected by D-Ala(2)-GIP, with an exception for resistin and insulin. The set of inflammatory genes were significantly decreased in adipose tissue in the D-Ala(2)-GIP injected animals on a chow diet. A DNA-microarray revealed that APO-genes and CYP-genes were affected by D-Ala(2)-GIP treatment in adipose tissue. These results suggest that the body weight-reducing effect of D-Ala(2)-GIP may be explained by lower LPL activity and insulin serum level. Moreover, the identified GIP candidate gene targets in adipose tissue link GIP action to lipid metabolism exerted by APO and CYP genes. (C) 2011 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)938-945
Number of pages8
JournalPeptides
Volume32
Issue number5
DOIs
Publication statusPublished - May-2011

Keywords

  • GIP
  • Insulin resistance
  • Type 2 diabetes
  • Adipose tissue
  • Lipid metabolism
  • DEPENDENT INSULINOTROPIC POLYPEPTIDE
  • LIPOPROTEIN-LIPASE
  • AMYLOID FIBRILS
  • ADIPOSE-TISSUE
  • IN-VIVO
  • A-II
  • OBESITY
  • MOUSE
  • EXPRESSION
  • RESISTANCE

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