Related Experiment Video
Updated: Nov 15, 2025
Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues
Published on: March 31, 2016
Oleanolic acid derivative HA-20 inhibits adipogenesis in a manner involving PPARγ-FABP4/aP2 pathway
Jie Wang1, Yuchao Zhang1, Qi Shen1
1State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation Centre of Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu, China.
Abstract:
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.
Insights
A novel oleanolic acid derivative, HA-20, effectively inhibits fat cell formation and reduces body weight in obesity models. This compound shows promise as a leading agent for developing new anti-obesity drugs.
Area of Science:
- Pharmacology and Natural Product Chemistry
- Metabolic Diseases and Obesity Research
Background:
- Obesity is a complex chronic disease linked to severe health issues like type II diabetes and heart disease.
- Current anti-obesity pharmacotherapies are limited, highlighting the need for novel therapeutic agents.
- Oleanolic acid (OA) derivatives represent a promising natural source for discovering anti-obesity compounds.
Purpose of the Study:
- To discover and characterize novel anti-obesity agents derived from oleanolic acid.
- To evaluate the efficacy of a newly identified compound, HA-20, in inhibiting adipogenesis both in vitro and in vivo.
Main Methods:
- Utilized 3T3-L1 preadipocytes for in vitro screening and differentiation assays.
- Established a high-fat diet (HFD)-induced obesity mouse model for in vivo studies.
- Conducted transcriptome analysis to identify gene expression changes and pathway analysis to elucidate the mechanism of action.
Main Results:
- Discovered HA-20, a novel OA derivative, potently suppressed 3T3-L1 adipogenesis without cytotoxicity.
- In vivo studies demonstrated that HA-20 reduced body weight and exhibited lipid-lowering effects in HFD-induced obese mice.
- Transcriptome analysis revealed HA-20 downregulates key adipogenesis/lipogenesis genes, including Pparg, Cebpa, Fas, Acc, and Fabp4/aP2, via the PPARγ-FABP4/aP2 pathway.
Conclusions:
- HA-20 exhibits significant anti-obesity potential by inhibiting adipogenesis and lipogenesis.
- The compound effectively targets the PPARγ-FABP4/aP2 pathway, offering a novel mechanism for combating obesity.
- HA-20 serves as a valuable lead compound for the development of next-generation anti-obesity therapeutics.
Related Concept Videos
01:25Lipid Catabolism
01:09GPCRs Regulate Adenylyl Cylase Activity
01:28Overview of Fatty Acid Metabolism
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...