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

doi:10.1038/s41598-021-86250-x

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^* (Corresponding Author)

^*Corresponding author for this work

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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 language	English
Article number	6949
Number of pages	14
Journal	Scientific Reports
Volume	11
DOIs	https://doi.org/10.1038/s41598-021-86250-x
Publication status	Published - 26 Mar 2021

Bibliographical note

Acknowledgements
P.J.V. was funded by a British Heart Foundation Ph.D. scholarship (FS/16/25/32136). This work was also sup- ported by the Medical Research Council (MR/L002620/1 to J.J.R.), the Biotechnology and Biological Sciences Research Council (BB/K017772/1 to J.J.R.), Diabetes UK (18/0005884 to J.J.R.) and the British Heart Foundation (PG/14/43/30889 to M.D.). The authors gratefully acknowledge the Microscopy and Histology core facility and the Medical Research Facility, University of Aberdeen for their support and assistance in this work.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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

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 inlipid 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.",

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

note = "Acknowledgements P.J.V. was funded by a British Heart Foundation Ph.D. scholarship (FS/16/25/32136). This work was also sup- ported by the Medical Research Council (MR/L002620/1 to J.J.R.), the Biotechnology and Biological Sciences Research Council (BB/K017772/1 to J.J.R.), Diabetes UK (18/0005884 to J.J.R.) and the British Heart Foundation (PG/14/43/30889 to M.D.). The authors gratefully acknowledge the Microscopy and Histology core facility and the Medical Research Facility, University of Aberdeen for their support and assistance in this work.",

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T1 - Phosphoprotein enriched in astrocytes (PEA)-15 is a novel regulator of adipose tissue expansion

AU - Verschoor, Pola Julia

AU - Greig, Fiona H

AU - Rochford, Justin

AU - Levate', Giovanni

AU - Delibegovic, Mirela

AU - Thompson, Dawn

AU - Leeson-Payne, Alasdair

AU - Dekeryte, Ruta

AU - Banks, Ruth

AU - Ramos, Joe W

AU - Nixon, Graeme

N1 - Acknowledgements P.J.V. was funded by a British Heart Foundation Ph.D. scholarship (FS/16/25/32136). This work was also sup- ported by the Medical Research Council (MR/L002620/1 to J.J.R.), the Biotechnology and Biological Sciences Research Council (BB/K017772/1 to J.J.R.), Diabetes UK (18/0005884 to J.J.R.) and the British Heart Foundation (PG/14/43/30889 to M.D.). The authors gratefully acknowledge the Microscopy and Histology core facility and the Medical Research Facility, University of Aberdeen for their support and assistance in this work.

PY - 2021/3/26

Y1 - 2021/3/26

N2 - 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 inlipid 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.

AB - 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 inlipid 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.

KW - Phosphoprotein enriched in astrocytes-15

KW - Adipose tissue

KW - Atherosclerosis

KW - Extracellular signal–regulated kinases 1/2

U2 - 10.1038/s41598-021-86250-x

DO - 10.1038/s41598-021-86250-x

M3 - Article

C2 - 33772049

SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

M1 - 6949

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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