Loss of prion protein is associated with the development of insulin resistance and obesity

Biochem J. 2017 Aug 17;474(17):2981-2991. doi: 10.1042/BCJ20170137.

Abstract

Prion protein (PrPC) was initially described due to its involvement in transmissible spongiform encephalopathies. It was subsequently demonstrated to be a cell surface molecule involved in many physiological processes, such as vesicle trafficking. Here, we investigated the roles of PrPC in the response to insulin and obesity development. Two independent PrPC knockout (KO) and one PrPC overexpressing (TG20) mouse models were fed high-fat diets, and the development of insulin resistance and obesity was monitored. PrPC KO mice fed high-fat diets presented all of the symptoms associated with the development of insulin resistance: hyperglycemia, hyperinsulinemia, and obesity. Conversely, TG20 animals fed high-fat diets showed reduced weight and insulin resistance. Accordingly, the expression of peroxisome proliferator-activated receptor gamma (PPARγ) was reduced in PrPC KO mice and increased in TG20 animals. PrPC KO cells also presented reduced glucose uptake upon insulin stimulation, due to reduced translocation of the glucose transporter Glut4. Thus, our results suggest that PrPC reflects susceptibility to the development of insulin resistance and metabolic syndrome.

Keywords: insulin resistance; obesity; prion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Cells, Cultured
  • Crosses, Genetic
  • Diet, High-Fat / adverse effects
  • Embryo, Mammalian / pathology
  • Female
  • Gene Expression Regulation
  • Glucose Transporter Type 4 / metabolism*
  • Insulin Resistance*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Obesity / etiology
  • Obesity / metabolism*
  • Obesity / pathology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • PrPC Proteins / genetics
  • PrPC Proteins / metabolism*
  • Prion Proteins / genetics
  • Prion Proteins / metabolism*
  • Protein Transport
  • Weight Gain

Substances

  • Glucose Transporter Type 4
  • PPAR gamma
  • PrPC Proteins
  • Prion Proteins
  • Prnp protein, mouse
  • Slc2a4 protein, mouse