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

PLoS One. 2012;7(7):e40156. doi: 10.1371/journal.pone.0040156. Epub 2012 Jul 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Diet, High-Fat
  • Energy Metabolism
  • Fatty Liver / prevention & control*
  • Gastric Inhibitory Polypeptide / biosynthesis*
  • Gastric Inhibitory Polypeptide / pharmacology
  • Glucose / metabolism*
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Homeostasis*
  • Insulin Resistance / physiology
  • Male
  • Mice
  • Mice, Transgenic
  • Obesity / etiology*
  • Obesity / metabolism

Substances

  • Gastric Inhibitory Polypeptide
  • Glucose