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OPA1-anchored PKA phosphorylates perilipin 1 on S522 and S497 in adipocytes differentiated from human adipose stem cells.

ABSTRACT: Optic atrophy 1 (OPA1) is the A-kinase anchoring protein targeting the pool of protein kinase A (PKA) responsible for perilipin 1 phosphorylation, a gatekeeper for lipolysis. However, the involvement of OPA1-bound PKA in the downstream regulation of lipolysis is unknown. Here we show up-regulation and relocation of OPA1 from mitochondria to lipid droplets during adipocytic differentiation of human adipose stem cells. We employed various biochemical and immunological approaches to demonstrate that OPA1-bound PKA phosphorylates perilipin 1 at S522 and S497 on lipolytic stimulation. We show that the first 30 amino acids of OPA1 are essential for its lipid droplet localization as is OMA1-dependent processing. Finally, our results indicate that presence of OPA1 is necessary for lipolytic phosphorylation of downstream targets. Our results show for the first time, to our knowledge, how OPA1 mediates adrenergic control of lipolysis in human adipocytes by regulating phosphorylation of perilipin 1.

SUBMITTER: Rogne M

PROVIDER: S-EPMC6014102 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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OPA1-anchored PKA phosphorylates perilipin 1 on S522 and S497 in adipocytes differentiated from human adipose stem cells.

Rogne Marie M Chu Dinh-Toi DT Küntziger Thomas M TM Mylonakou Maria-Niki MN Collas Philippe P Tasken Kjetil K

Molecular biology of the cell 20180424 12

Optic atrophy 1 (OPA1) is the A-kinase anchoring protein targeting the pool of protein kinase A (PKA) responsible for perilipin 1 phosphorylation, a gatekeeper for lipolysis. However, the involvement of OPA1-bound PKA in the downstream regulation of lipolysis is unknown. Here we show up-regulation and relocation of OPA1 from mitochondria to lipid droplets during adipocytic differentiation of human adipose stem cells. We employed various biochemical and immunological approaches to demonstrate tha ...[more]

PMID: 29688805

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Project description:Squalene (Sq) is a natural compound, found in various plant oils, algae, and larger quantity in deep-sea shark liver. It is also known as an intermediate of cholesterol synthesis in plants and animals including humans. Although evidences demonstrated its antioxidant, anticancer, hypolipidemic, and hepatoprotective and cardioprotective effects, its biological effects in cellular function might have been underestimated because of the water-insoluble property. To overcome this hydrophobicity, we synthesized new amphiphilic Sq derivative (HH-Sq). On the other hand, adipose-derived stem cells (ASCs) are a valuable source in regenerative medicine for its ease of accessibility and multilineage differentiation potential. Nevertheless, impaired cellular functions of ASCs derived from diabetic donor have still been debated controversially. In this study, we explored the effect of the HH-Sq in comparison to Sq on the adipocyte differentiation of ASCs obtained from subjects with type 2 diabetes. Gene expression profile by microarray analysis at 14 days of adipogenic differentiation revealed that HH-Sq induced more genes involved in intracellular signaling processes, whereas Sq activated more transmembrane receptor pathway-related genes. In addition, more important number of down-regulated and up-regulated genes by Sq and HH-Sq were not overlapped, suggesting the compounds might not only have difference in their chemical property but also potentially exert different biological effects. Both Sq and HH-Sq improved metabolism of adipocytes by enhancing genes associated with energy homeostasis and insulin sensitivity, SIRT1, PRKAA2, and IRS1. Interestingly, Sq increased significantly early adipogenic markers and lipogenic gene expression such as PPARG, SREBF1, and CEBPA, but not HH-Sq. As a consequence, smaller and fewer lipid droplet formation was observed in HH-Sq-treated adipocytes. Based on our findings, we report that both Sq and HH-Sq improved adipocyte metabolism, but only HH-Sq prevented excessive lipogenesis without abrogating adipocyte differentiation. The beneficial effect of HH-Sq provides an importance of synthesized derivatives from a natural compound with therapeutic potentials in the application of cell therapies.

Dataset Information

OPA1-anchored PKA phosphorylates perilipin 1 on S522 and S497 in adipocytes differentiated from human adipose stem cells.

Publications

OPA1-anchored PKA phosphorylates perilipin 1 on S522 and S497 in adipocytes differentiated from human adipose stem cells.

Similar Datasets

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