Phosphoprotein enriched in astrocytes (PEA)-15 is a novel regulator of adipose tissue expansion

Pola Julia Verschoor, Fiona H Greig, Justin Rochford, Giovanni Levate', Mirela Delibegovic, Dawn Thompson, Alasdair Leeson-Payne, Ruta Dekeryte, Ruth Banks, Joe W Ramos, Graeme Nixon

Research output: Contribution to journalArticlepeer-review

Abstract

Excessive expansion of adipose tissue in obesity typically leads to overflow and accumulation of lipids in other tissues, causing fatty liver disease and atherosclerosis. The intracellular protein, Phosphoprotein Enriched in Astrocytes (PEA)-15 has been linked to metabolic disease but its role in
lipid storage has not been examined. To delineate the role of PEA-15 in adipose tissue, we placed PEA-15-/- mice on a high fat diet. These mice developed increased body weight and greater white adipose tissue expansion compared to high fat diet-fed wild type mice. This was due to increased adipocyte cell size in PEA-15-/- mice consistent with greater lipid storage capacity. Surprisingly, PEA-15-/- mice exhibited improvements in whole body insulin sensitivity, lower hepatic weight and decreased serum triglycerides indicating a protective phenotype. To determine effects on atherosclerosis, PEA-15-/- mice were crossed with the ApoE-/- mice on a high fat diet. Strikingly, these mice were protected from atherosclerosis and had less hepatic lipid accumulation despite increased adiposity. Therefore, we reveal for the first time that PEA-15 plays a novel role in regulating the expansion of adipose tissue. Decreasing PEA-15 expression increases the sequestering of lipids in adipose tissue, protecting other tissues in obesity, thereby improving metabolic health.
Original languageEnglish
Article number6949
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 26 Mar 2021

Keywords

  • Phosphoprotein enriched in astrocytes-15
  • Adipose tissue
  • Atherosclerosis
  • Extracellular signal–regulated kinases 1/2

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