Peng Li’s lab publishes an article in “Diabetes” demonstrating the role of lipid droplets and associated cellular organelles in regulating energy expenditure in adipocytes2018-07-18 13:26:32
Metabolic homeostasis is maintained by an interplay among tissues, organs, intracellular organelles, and molecules. Excessive lipid storage (obesity) and the failure to store lipids in adipose tissues (lipodystrophy) both contribute to metabolic disorders, although these disorders are associated with opposite fat storage phenotypes. In addition to maintaining an appropriate amount of adipose tissues, fat tissue types and their interactions, including WAT as an energy storage site and brown adipose tissue (BAT) and beige adipose tissue as energy burning sites, are important in systemic lipid metabolism. At cellular level, the interaction between lipid droplets (LDs) and other organelles in adipocytes also contributes to cellular lipid homeostasis, including metabolic flux and fatty acids availability. Therefore, the balance and coordination of adipocyte types and subcellular organelles are important in maintaining systemic metabolic homeostasis.
Cidea and Cidec are lipid droplet (LD)-associated proteins that promote lipid storage in brown and white adipose tissue (BAT and WAT, respectively). Using ob/ob/Cidea-/-, ob/ob/Cidec-/-, and ob/ob/Cidea-/-/Cidec-/- mouse models and CIDE-deficient cells, we studied metabolic regulation during severe obesity to identify ways to maintain metabolic homeostasis and promote antiobesity effects. The phenotype of ob/ob/Cidea-/- mice was similar to that of ob/ob mice in terms of serum parameters, adipose tissues, lipid storage and gene expression. Typical lipodystrophy accompanied by insulin resistance occurred in ob/ob/Cidec-/- mice, with ectopic storage of lipids in the BAT and liver. Interestingly, double deficiency of Cidea and Cidec activated both WAT and BAT to consume more energy and increase insulin sensitivity compared to their behavior in the other three mouse models. Increased lipolysis, which occurred on the LD surfaces and released fatty acids led to activated β-oxidation and oxidative phosphorylation in peroxisomes and mitochondria in CIDE-deficient adipocytes. The coordination among LDs, peroxisomes and mitochondria was regulated by ATGL-PPARα. Double deficiency of Cidea and Cidec activated energy consumption in both WAT and BAT, which provided new insights into therapeutic approaches for obesity and diabetes.
Dr. Linkang Zhou and PhD candidate Miao Yu are the co-first authors. Dr. Peng Li and Dr. Li Xu are co-corresponding authors. This study was supported by the National Natural Science Foundation of China, National Basic Research Program, State Key Laboratory of Membrane Biology and the Tsinghua-Peking Joint Center for Life Sciences.
Figure: Role of CIDE-ATGL-PPARα in regulating energy expenditure in adipotytes