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

• Published in: Biochemical journal Vol. 474; no. 17; p. 2981
• Main Authors: de Brito, Giovanna, Lupinacci, Fernanda C, Beraldo, Flávio H, Santos, Tiago G, Roffé, Martín, Lopes, Marilene H, de Lima, Vladmir C, Martins, Vilma R, Hajj, Glaucia N
• Format: Journal Article
• Language: English
• Published: England 01-09-2017
• Subjects: 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; Prion Proteins - genetics; Prion Proteins - metabolism; Protein Transport; PrPC Proteins - genetics; PrPC Proteins - metabolism; Weight Gain; prion; insulin resistance; obesity
• ISSN: 1470-8728
• DOI: 10.1042/BCJ20170137

Prion protein (PrP
) 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 PrP
in the response to insulin and obesity development. Two independent PrP
knockout (KO) and one PrP
overexpressing (TG20) mouse models were fed high-fat diets, and the development of insulin resistance and obesity was monitored. PrP
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 PrP
KO mice and increased in TG20 animals. PrP
KO cells also presented reduced glucose uptake upon insulin stimulation, due to reduced translocation of the glucose transporter Glut4. Thus, our results suggest that PrP
reflects susceptibility to the development of insulin resistance and metabolic syndrome.