Loss of CD36 impairs hepatic insulin signaling by enhancing the interaction of PTP1B with IR.

Abstract

A contradictory role of CD36 in insulin resistance was found to be related to the nutrient state. Here, we examined that the physiological functions of CD36 in insulin signal transduction in mice fed a low-fat diet. CD36 deficiency led to hepatic insulin resistance and decreased insulin-stimulated tyrosine phosphorylation of insulin receptor β (IRβ) in mice fed a low-fat diet. The ability of insulin to bind with IR did not differ between WT and CD36-deficient hepatocytes. CD36 formed a complex with IRβ and dissociation of CD36/Fyn complex or inhibition of Fyn only partially reversed the effects of CD36 on hepatic insulin signaling. Furthermore, we found that CD36 deficiency led to abnormally increased hepatic protein-tyrosine phosphatase 1B (PTP1B) expression and enhanced PTP1B and IR interactions, which contributed to the decreased insulin signaling and disordered glucose metabolism. In addition, increased endoplasmic reticulum (ER) stress was found in the livers of the CD36-deficient mice, while inhibited ER stress normalized the PTP1B expression and restored insulin signaling in the CD36-deficient mice. Our findings suggest that the loss of CD36 impairs hepatic insulin signaling by enhancing the PTP1B/IR interaction that is induced by ER stress, indicating a possible critical step in the progression of hepatic insulin resistance.

• Authors: Ping Yang, Han Zeng, Wei Tan, Xiaoqing Luo, Enze Zheng, Lei Zhao, Li Wei, Xiong Z Ruan, Yao Chen, Yaxi Chen
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 34 Issue 4 Pg. 5658-5672 (04 2020) ISSN: 1530-6860 [Electronic] United States
• PMID: 32100381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Federation of American Societies for Experimental Biology.

Chemical References

• CD36 Antigens
• Cd36 protein, mouse
• Insulin
• Receptor, Insulin
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Ptpn1 protein, mouse

Topics

• Animals
• CD36 Antigens (physiology)
• Endoplasmic Reticulum Stress
• Female
• Insulin (metabolism)
• Insulin Resistance
• Liver (metabolism, pathology)
• Male
• Mice
• Mice, Knockout
• Protein Tyrosine Phosphatase, Non-Receptor Type 1 (genetics, metabolism)
• Receptor, Insulin (genetics, metabolism)
• Signal Transduction