GIP-Overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis

Su Jin Kim, Cuilan Nian, Subashini Karunakaran, Susanne M. Clee, Carlos M Isales, Christopher H.S. McIntosh

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Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert β-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM). In the present study, we tested the hypothesis that chronically elevating GIP levels in a transgenic (Tg) mouse model would increase adipose tissue expansion and exert beneficial effects on glucose homeostasis. In contrast, although GIP Tg mice demonstrated enhanced β-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. Adipose tissue macrophage infiltration and hepatic steatosis were both greatly reduced, and a number of genes involved in lipid metabolism/inflammatory signaling pathways were found to be down-regulated. Reduced adiposity in GIP Tg mice was associated with decreased energy intake, involving overexpression of hypothalamic GIP. Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis.

Original languageEnglish (US)
Article numbere40156
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 3 2012

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gastric inhibitory polypeptide
Nutrition
homeostasis
obesity
Homeostasis
Obesity
Diet
Glucose
Peptides
glucose
mice
diet
genetically modified organisms
adipocytes
adipose tissue
Transgenic Mice
gastrointestinal hormones
Adipocytes
insulin secretion
fatty liver

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

GIP-Overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. / Kim, Su Jin; Nian, Cuilan; Karunakaran, Subashini; Clee, Susanne M.; Isales, Carlos M; McIntosh, Christopher H.S.

In: PloS one, Vol. 7, No. 7, e40156, 03.07.2012.

Research output: Contribution to journalArticle

Kim, Su Jin ; Nian, Cuilan ; Karunakaran, Subashini ; Clee, Susanne M. ; Isales, Carlos M ; McIntosh, Christopher H.S. / GIP-Overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. In: PloS one. 2012 ; Vol. 7, No. 7.
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