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P2Y2 Receptor Facilitates High‐fat diet Induced Insulin Resistance
Author(s) -
Kishore Bellamkonda,
Zhang Yue,
Heiney Kristina,
Ecelbarger Carolyn
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.805.7
Subject(s) - medicine , endocrinology , insulin resistance , insulin receptor , white adipose tissue , glut4 , insulin , adipose tissue , inflammation , irs1 , insulin receptor substrate , biology , chemistry
Development of insulin resistance (IR) in obesity is attributed to inflammation and lipotoxicity in white adipose tissue (WAT), among other factors. We observed that genetic deletion of P2Y 2 ‐R confers significant resistance to development of high‐fat diet (HFD)‐induced obesity and improves glucose tolerance. P2Y 2 ‐R is expressed in all the key organs involved or potentially contributing to IR (WAT, liver, skeletal muscle, kidney, intestines, and pancreas). Hence, we hypothesized that P2Y 2 ‐R may facilitate diet‐induced IR, and investigated insulin signaling and inflammation in WAT of wild type (WT) and P2Y 2 ‐R knockout (KO) mice fed HFD. Groups of age‐matched adult WT and KO mice were fed regular diet (10% calories as fat; n = 6) or HFD (60% calories as fat; n = 14) with free access to food and water for 16 weeks and euthanized. An insulin sensitivity test (IST) was conducted prior to euthanasia. WAT was collected and processed for the mRNA expression of key molecules involved in inflammation and insulin sensitivity. The expression of P2Y 2 ‐R in WAT was increased by 2‐fold in HFD‐fed WT mice. Whole‐body insulin sensitivity, and the mRNA expression of the insulin receptor, GLUT4 and IRS‐1 (insulin receptor substrate‐1) in WAT were significantly higher in HFD fed KO mice vs. WT mice. On the contrary, the expression of pro‐inflammatory molecules IL‐6, MCP‐1, CCR2, CD68 and F4/80 were significantly higher in WAT of HFD fed WT vs. KO mice. Our results demonstrate that KO of the P2Y 2 ‐R is protective against diet‐induced obesity and IR. The mechanisms may involve higher expression of insulin receptor signaling proteins, as well as reduced inflammation and lipotoxicity in the WAT of the KO mice .