Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in mice

Biochem Biophys Res Commun. 2008 Nov 7;376(1):21-5. doi: 10.1016/j.bbrc.2008.08.052. Epub 2008 Aug 22.


Gastric inhibitory polypeptide (GIP) is an incretin and directly promotes fat accumulation in adipocytes. Inhibition of GIP signaling prevents onset of obesity and increases fat oxidation in peripheral tissues under high-fat diet (HFD), but the mechanism is unknown. In the present study, we investigated the effects of inhibition of GIP signaling on adiponectin levels after 3 weeks of HFD by comparing wild-type (WT) mice and GIP receptor-deficient (Gipr(-/-)) mice. In HFD-fed Gipr(-/-) mice, fat oxidation was significantly increased and adiponectin mRNA levels in white adipose tissue and plasma adiponectin levels were significantly increased compared to those in HFD-fed WT mice. In addition, the PPARalpha mRNA level was increased and the ACC mRNA level was decreased in skeletal muscle of HFD-fed Gipr(-/-) mice compared with those in HFD-fed WT mice. These results indicate that inhibition of GIP signaling increases adiponectin levels, resulting in increased fat oxidation in peripheral tissues under HFD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Adipose Tissue, White / metabolism
  • Animals
  • Body Weight
  • Diet
  • Dietary Fats / administration & dosage*
  • Gastric Inhibitory Polypeptide / antagonists & inhibitors*
  • Gastric Inhibitory Polypeptide / genetics
  • Gastric Inhibitory Polypeptide / metabolism
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • RNA, Messenger
  • Signal Transduction


  • Adiponectin
  • Dietary Fats
  • PPAR alpha
  • RNA, Messenger
  • Gastric Inhibitory Polypeptide