Drug Design, Development and Therapy (Dec 2020)
The Inhibitory Effects of Juglanin on Adipogenesis in 3T3-L1 Adipocytes
Abstract
Guang Wang,1,* Bing Wu,2,* Wenzhou Xu,3 Xuefei Jin,4 Kun Wang,5 Heyuan Wang6 1Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 2Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 3Department of Periodontology, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130033, People’s Republic of China; 4Department of Urology, China-Japan Union Hospital of Jilin University, Jilin Key Laboratory of Urologic Oncology, Changchun, Jilin 130033, People’s Republic of China; 5Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 6Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heyuan WangDepartment of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaTel/Fax +86-431-88782222Email [email protected]: Deregulation of adipogenesis plays an important role in obesity and other metabolism disorders. PPAR, C/EBP and SREBP1c are key transcriptional factors involved in adipogenesis and lipogenesis. Juglanin is a natural compound belonging to flavonoids, and it has been reported that juglanin has a potent inhibitory effect on inflammation and certain type of cancers. However, the effects of juglanin in adipogenesis have not been reported before.Materials and Methods: 3T3-L1 preadipocytes were incubated with differentiation induction medium in the presence or absence of 0.5, 2.5, or 5 μM juglanin for an 8-day differentiation period. The lipid droplets accumulated in the cytoplasm were monitored by Oil Red O staining on days 0, 2, 5, and 8. The regulatory effects of juglanin on adipogenesis-related genes and proteins were investigated by real-time polymerase chain reaction and Western blot analysis.Results: Juglanin significantly decreased lipid accumulation in differentiated adipocytes. Our findings show that juglanin reduced the expression of C/EBPα, C/EBPβ, and SREBP-1c without affecting PPARα or PPARγ expression. Additionally, juglanin increased the activation of the SIRT1/AMPK signaling pathway through the phosphorylation of AMPKα. Finally, we performed an AMPK inhibitor experiment, which revealed that the inhibitory effects of juglanin on adipogenesis are mediated through AMPK.Discussion: Juglanin can prevent adipogenesis by suppressing lipid accumulation and the differentiation of preadipocytes. The mechanism of juglanin regulating adipogenesis requires further investigation. Future clinical study in vivo could shed more light on its implication in modulating obesity and metabolic disorders.Keywords: Juglanin, adipogenesis, obesity, lipid metabolism, AMPK
