Oleanolic acid derivative HA-20 inhibits adipogenesis in a manner involving PPARγ-FABP4/aP2 pathway
| Autor: | Yu-Chao Zhang, Qi Shen, Jie Wang, Jian-Xin Li, Jing Wu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Peroxisome proliferator-activated receptor gamma Cell Down-Regulation 030209 endocrinology & metabolism Pharmacology Diet High-Fat Fatty Acid-Binding Proteins Transcriptome Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology In vivo 3T3-L1 Cells Nonalcoholic fatty liver disease Adipocytes medicine Animals Oleanolic Acid Molecular Biology Oleanolic acid Hypolipidemic Agents Adipogenesis medicine.disease Mice Inbred C57BL PPAR gamma 030104 developmental biology medicine.anatomical_structure Liver chemistry Lipogenesis Signal Transduction |
| Zdroj: | Journal of Molecular Endocrinology. 66:245-258 |
| ISSN: | 1479-6813 0952-5041 |
| DOI: | 10.1530/jme-20-0075 |
| Popis: | Obesity is a chronic disease that increases the risk of type II diabetes, heart diseases and nonalcoholic fatty liver disease. Unfortunately, to date, only a handful of drugs are approved for clinical use. This study aims at the discovery of anti-obesity agents based on naturally sourced oleanolic acid (OA) derivatives. 3T3-L1 preadipocytes were differentiated into mature adipocytes for in vitro assays, and a high-fat diet (HFD)-induced obesity mice model was established for in vivo studies. The screening of the OA derivatives was performed with 3T3-L1 cell, and resulted in a discovery of a novel compound HA-20 with a potent inhibitory activity on 3T3-L1 adipogenesis. In vitro data demonstrated that HA-20 markedly suppressed the adipogenesis in 3T3-L1 at the early stage without cytotoxicity. In vivo research using HFD mice revealed that HA-20 lowered the body weight, and possessed a lipid-lowering effect. Transcriptome analysis discovered that the mainly adipogenesis/lipogenesis genes regulated by HA-20 were Pparg, Cebpa, Fas, Acc, and Fabp4/aP2. Mechanism study revealed that HA-20 played its bioactive roles at least via downregulating PPARγ-FABP4/aP2 pathway in 3T3-L1, which was further confirmed in HFD-induced obesity mice. Our findings provided a new insight into fighting fat accumulation based on OA derivatives, and demonstrated that HA-20 may sever as a worthy leading compound for the further development of anti-obesity agents. |
| Databáze: | OpenAIRE |
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