APPL1 knockdown blocks adipogenic differentiation and promotes adipocyte lipolysis
| Autor: | Zhongyuan Wen, Junfeng Li, Yemin Zhang, Yalin Fu, Changhua Wang, Zhao Tang, Yingkang Cao, Deling Zhang, Mingxin Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Lipolysis Down-Regulation 030209 endocrinology & metabolism Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Insulin resistance Adipocyte 3T3-L1 Cells MG132 medicine Adipocytes Autophagy Animals RNA Small Interfering Molecular Biology Cells Cultured Adaptor Proteins Signal Transducing Adipogenesis Adiponectin biology Cell Differentiation medicine.disease Cell biology Mice Inbred C57BL Insulin receptor 030104 developmental biology chemistry Gene Knockdown Techniques biology.protein Thermogenesis |
| Zdroj: | Molecular and cellular endocrinology. 506 |
| ISSN: | 1872-8057 |
| Popis: | Adipocyte dysfunction is closely associated with the development of obesity, insulin resistance, and type 2 diabetes. In addition to having a positive effect on adiponectin pathway and insulin signaling through direct and/or indirect mechanisms, adapter protein APPL1 has also been reported to regulate body weight, brown fat tissues thermogenesis, and body fat distribution in diabetic individuals. However, there is dearth of data on the specific role of APPL1 on adipogenic differentiation and adipocyte lipolysis. In this study, APPL1's function in adipocyte differentiation and adipocyte lipolysis was evaluated, and the possible mechanisms were investigated. We found that APPL1 knockdown (KD) impeded differentiation of 3T3-L1 preadipocytes into mature 3T3-L1 adipocytes and enhanced basal and insulin-suppressed lipolysis in mature 3T3-L1 adipocytes. APPL1 KD cells presented a reduced autophagic activity in 3T3-L1 preadipocytes and mature 3T3-L1 adipocytes. In 3T3-L1 preadipocytes, APPL1 KD reduced PPARγ protein levels, which was prevented by administration with proteasome inhibitor MG132. Furthermore, APPL1 KD-reduced autophagic activity in mature 3T3-L1 adipocytes was markedly restored by inhibition of PKA, accompanied with prevention of APPL1-induced lipolysis. In addition, APPL1 KD caused insulin resistance in mature 3T3-L1 adipocytes. Unexpectedly, we found that APPL1 overexpression did not appear to play a role in adipogenic differentiation and adipocyte lipolysis. Our results confirmed that APPL1 KD inhibits adipogenic differentiation by suppressing autophagy and enhances adipocyte lipolysis through activating PKA respectively. These findings may deepen our understanding of APPL1 function, especially its regulation on adipocyte biology. |
| Databáze: | OpenAIRE |
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