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Background: Recently, the role of autophagy in glucose and lipid metabolism has been emerging. Mice experiments showed that autophagy deficiency could prevent diet-induced obesity, characterized by less fat and a browning phenotype of white adipocyte (WAT). However, the underlying molecular mechanism is not well explored and the data from human are limited. Method: The mRNA sequencing data of undifferentiated and differentiated human adipocyte cell lines, including two white adipocyte (WAT) and one brown adipocyte (BAT) were included in our analysis. Gene expression was reduced by RNA interference in human adipocyte and was enhanced by glucocorticoid, respectively. Qualifying the lipid droplet content and quantifying the adipolysis and differentiation marker expression were applied to evaluate WAT differentiation. LC3 was used as a marker to examine autophagy function of adipocyte. Result: we found a remarkable feature of adipocyte differentiation that inflammation signaling was significantly strengthened during WAT maturation, but not during BAT maturation. The alteration of Zinc Finger protein 36 (ZFP36), which mediates the decay of mRNA transcripts of inflammation molecules, obviously affected the phenotype of mature WAT: silencing of ZFP36 gene resulted in a more whitening phenotype and induction of ZFP36 resulted in a browning phenotype. ZFP36 activity was associated with p38 MAPK signaling that was regulated by autophagy. Conclusion: ZFP36 links autophagy to the determination of mature adipocyte phenotype. Therefore, ZFP36 is a potential target to prevent obesity and improve glucose and lipid metabolism.