Dataset Information

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.

SUBMITTER: Luo X

PROVIDER: S-EPMC7281849 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Luo Xiaoxiao X Li Yanping Y Yang Ping P Chen Yao Y Wei Li L Yu Ting T Xia Jun J Ruan Xiong Z XZ Zhao Lei L Chen Yaxi Y

EBioMedicine 20200606

<h4>Background</h4>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.<h4>Methods</h4>Using visceral adipose tissue from obese patients, a high-fat diet ...[more]

PMID: 32516742

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Dataset Information

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

Background

Methods

Findings

Interpretation

Publications

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

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