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

EBioMedicine
Xiaoxiao LuoYaxi Chen

Abstract

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. 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. 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 accumula...Continue Reading

Citations

Aug 6, 2020·International Journal of Molecular Sciences·Álvaro González-DomínguezAlfonso María Lechuga-Sancho
Jun 2, 2021·Journal of Cellular and Molecular Medicine·Qiang ZhangYuanyi Yue

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Methods Mentioned

BETA
co-immunoprecipitation
PCR
reactive oxygen species assay
Co-IP

Key Resources (RRID) Mentioned

AB_11153320
AB_1645199
AB_2737732
AB_10894582
CVCL_0123
AB_522498
AB_10003498
AB_2571576
AB_2571577
AB_10700003

Software Mentioned

ImageJ

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