title: Sub-chronic administration of stable GIP analog in mice decreases serum LPL activity and body weight.
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-1β, TNFα, 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.
authors.affiliation: Centre for Medical Biomics, UMCG, University of Groningen, The Netherlands. ewa.szalowska@wur.nl
authors.forename: Ewa
authors.initials: E
authors.lastname: Szalowska
authors.forename: Kees
authors.initials: K
authors.lastname: Meijer
authors.forename: Niels
authors.initials: N
authors.lastname: Kloosterhuis
authors.forename: Farhad
authors.initials: F
authors.lastname: Razaee
authors.forename: Marion
authors.initials: M
authors.lastname: Priebe
authors.forename: Roel J
authors.initials: RJ
authors.lastname: Vonk
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D004041:Dietary Fats / Q000633:toxicity; D005749:Gastric Inhibitory Polypeptide / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000097:blood* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D052243:Resistin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D015850:Interleukin-6; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha; D005749:Gastric Inhibitory Polypeptide; D008071:Lipoprotein Lipase