Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00062)
Name
Obesity
ICD
ICD-11: 5B81
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Obesity [ICD-11: 5B81]
Responsed Drug Atorvastatin Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell senescence
In Vivo Model
Mice were sacrificed by cervical dislocation. As described previously, epidydimal adipose tissues (EAT) were isolated and minced into ~5-mg pieces in DMEM containing 10% FBS. After 2 h of incubation, 50 mg of small pieces were placed in serum-free DMEM and exposed to 1 umol/L atorvastatin for 18 h, and 0.1% DMSO served as a control. In specific experiments, EAT explants were also treated with GGPP (50 uM; GlpBio), or ferrostatin-1 (Fer-1, 8 uM), and added to the culture medium at the same time as was atorvastatin. Group animal size was n = 6-8 per group. The exact group size is specially described in the Figure legends.

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Response regulation Atorvastatin decreased the level of GPX4 and depleted GGPP production, but not Fer-1. Atorvastatin was able to induce ferroptosis in adipose tissue, which was due to increased ROS and an increase in cellular senescence. Moreover, this effect could be reversed by the supplement of GGPP. Taken together, our results suggest that the induction of ferroptosis contributed to statin-induced cell senescence in adipose tissue and may contributed to obesity disease.
References
Ref 1 Statin-Induced Geranylgeranyl Pyrophosphate Depletion Promotes Ferroptosis-Related Senescence in Adipose Tissue. Nutrients. 2022 Oct 18;14(20):4365. doi: 10.3390/nu14204365.