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The Mevalonate Pathway Is Indispensable for Adipocyte Survival
Yu-Sheng Yeh1, Huei-Fen Jheng1, Mari Iwase1
1Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Iscience
|November 6, 2018
Summary
The mevalonate pathway is crucial for adipocyte function. Disrupting it causes severe metabolic issues and cell death, highlighting its role in regulating fat tissue turnover.
Area of Science:
- Biochemistry
- Metabolic Disease
- Adipose Tissue Biology
Background:
- The mevalonate pathway synthesizes isoprenoids and cholesterol, vital for cellular functions.
- Adipose tissue stores cholesterol, but the role of its local mevalonate pathway is poorly understood.
Purpose of the Study:
- To investigate the function of the mevalonate pathway in adipose tissue.
- To determine the impact of disrupting this pathway on adipocyte biology and overall metabolism.
Main Methods:
- Generation of adipose-specific 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR) knockout (aKO) mice.
- Analysis of metabolic parameters, lipodystrophy, and hepatomegaly in aKO mice.
- In vitro studies on HMGCR-disrupted adipocytes with supplementation of pathway intermediates.
Main Results:
- aKO mice exhibited severe lipodystrophy, glucose/lipid metabolic disorders, and hepatomegaly.
- Metabolic abnormalities were reversed upon fat transplantation.
- HMGCR disruption in adipocytes led to lipid accumulation loss and increased cell death, partially rescued by mevalonate and geranylgeranyl pyrophosphate.
Conclusions:
- The mevalonate pathway is essential for adipocyte lipid homeostasis and survival.
- Down-regulation of HMGCR induces adipocyte apoptosis.
- The mevalonate pathway is a key regulator of adipocyte turnover and adipose tissue function.
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