Obesity induces preadipocyte CD36 expression promoting inflammation via the disruption of lysosomal calcium homeostasis and lysosome function.

Abstract

BACKGROUND:

Preadipocyte is closely related to obesity-induced inflammation. The impairment of autophagic flux by defective lysosomal function has been observed in adipose tissue from obese mice. While the fatty acid translocase CD36 is an important immuno-metabolic receptor, it remains unclear whether preadipocyte CD36 is involved in adipose tissue inflammation and whether CD36 regulates lysosomal function.

METHODS:

Using visceral adipose tissue from obese patients, a high-fat diet (HFD)-induced obese mice model, primary mouse preadipocytes and 3T3L1 cells we analyzed whether and how preadipocyte CD36 modulates lysosomal function and adipose tissue inflammation.

FINDINGS:

CD36 expression in preadipocytes is induced in obese patients and HFD-fed mice, accompanied with the disruption of lysosome function. CD36 knockout protects primary preadipocytes of HFD-fed mice from lysosomal impairment. In vitro, CD36 interacts with Fyn to phosphorylate and activate Inositol (1,4,5)-trisphosphate receptor 1 (IP3R1), causing excess calcium transport from endoplasmic reticulum (ER) to lysosome, which results in lysosomal impairment and inflammation. Moreover, IP3R inhibitor 2-aminoethoxydiphenyl borate (2APB) attenuates lysosomal impairment, inflammation and lipid accumulation in CD36-overexpressing preadipocytes.

INTERPRETATION:

Our data support that the abnormal upregulation of CD36 in preadipocytes may contribute to the development of adipose tissue inflammation. CD36/Fyn/IP3R1-mediated lysosomal calcium overload leads to lysosomal impairment and inflammation in preadipocyte. Thus targeting improving lysosomal calcium homeostasis may represent a novel strategy for treating obesity-induced inflammation.

• Authors: Xiaoxiao Luo, Yanping Li, Ping Yang, Yao Chen, Li Wei, Ting Yu, Jun Xia, Xiong Z Ruan, Lei Zhao, Yaxi Chen
• Journal: EBioMedicine (EBioMedicine) Vol. 56 Pg. 102797 (Jun 2020) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 32516742 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• CD36 Antigens
• CD36 protein, human
• FYN protein, human
• Proto-Oncogene Proteins c-fyn
• Calcium

Topics

• 3T3 Cells
• Adipocytes (cytology, metabolism)
• Animals
• CD36 Antigens (genetics, metabolism)
• Calcium (metabolism)
• Cells, Cultured
• Cross-Sectional Studies
• Diet, High-Fat (adverse effects)
• Disease Models, Animal
• Female
• Gene Knockout Techniques
• Homeostasis
• Humans
• Lysosomes (metabolism)
• Male
• Mice
• Obesity (chemically induced, genetics, metabolism)
• Phosphorylation
• Primary Cell Culture
• Proto-Oncogene Proteins c-fyn (metabolism)
• THP-1 Cells