A New Fungal Triterpene from the Fungus Aspergillus flavus Stimulates Glucose Uptake without Fat Accumulation.
Dan-Dan LiYing WangEun La KimJongki HongJee H JungPublished in: Marine drugs (2022)
Through activity-guided fractionation, a new triterpene (asperflagin, 1 ) was isolated as a PPAR-γ agonist from the jellyfish-derived fungus Aspergillus flavus . Asperflagin displayed selective and moderate transactivation effects on PPAR-γ in Ac2F rat liver cells. Based on further biological evaluation and molecular docking analysis, we postulated that asperflagin might function as a PPAR-γ partial agonist. This compound was calculated to display a typical PPAR-γ ligand-receptor interaction that is distinct from that of full agonistic antidiabetics such as rosiglitazone, and may retain the antidiabetic effect without accompanying weight gain. Weight gain and obesity are typical side effects of the PPAR-γ full agonist rosiglitazone, and lead to suboptimal outcomes in diabetic patients. Compared to rosiglitazone, asperflagin showed higher glucose uptake in HepG2 human liver cells at concentrations of 20 and 40 μM but induced markedly lower adipogenesis and lipid accumulation in 3T3-L1 preadipocytes. These results suggest that asperflagin may be utilized for further study on advanced antidiabetic leads.
Keyphrases
- weight gain
- insulin resistance
- body mass index
- molecular docking
- birth weight
- induced apoptosis
- fatty acid
- cell cycle arrest
- weight loss
- adipose tissue
- high fat diet induced
- oxidative stress
- skeletal muscle
- endoplasmic reticulum stress
- molecular dynamics simulations
- type diabetes
- blood glucose
- high glucose
- blood pressure
- high intensity
- diabetic rats
- preterm birth
- data analysis
- gestational age