Objective: The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia (CAC) by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer (GC)-associated adipocytes. Methods: Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ, C/EPBα, PPARγ, and UCP1 in adipose mesenchymal stem cells (A-MSCs) to evaluate the function of exosomal miR-155. BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs. Results: Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets. Similarly, A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression (P < 0.05). Mechanistically, exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ, accompanied by downregulated C/EPBα and PPARγ and upregulated UCP1 (P < 0.05). Moreover, overexpression of miR-155 in GC exosomes improved CAC in vivo, which was characterized by fat loss, suppressed expressions of C/EPBβ, C/EPBα, and PPARγ in A-MSCs, and high expression of UCP1 (P < 0.05). Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects. Conclusions: GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβ of A-MSCs, which played a crucial role in CAC.

Ying Liu;Meng Wang;Ting Deng;Rui Liu;Tao Ning;Ming Bai;Guoguang Ying;Haiyang Zhang;Yi Ba

Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin's Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin 300060,China

癌症生物学与医学（英文版）

[1]Ying Liu;Meng Wang;Ting Deng;Rui Liu;Tao Ning;Ming Bai;Guoguang Ying;Haiyang Zhang;Yi Ba-.Exosomal miR-155 from gastric cancer induces cancer-associated cachexia by suppressing adipogenesis and promoting brown adipose differentiation via C/EPBβ)[J].癌症生物学与医学（英文版）,2022(09):1301-1314

adipodifferentiation

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