Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation

Research output: Contribution to journalJournal articlepeer-review

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Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation. / Stocks, Ben; Gonzalez-Franquesa, Alba; Borg, Melissa L.; Björnholm, Marie; Niu, Lili; Zierath, Juleen R; Deshmukh, Atul S.

In: Molecular and Cellular Proteomics, Vol. 21, No. 3, 100207, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Stocks, B, Gonzalez-Franquesa, A, Borg, ML, Björnholm, M, Niu, L, Zierath, JR & Deshmukh, AS 2022, 'Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation', Molecular and Cellular Proteomics, vol. 21, no. 3, 100207. https://doi.org/10.1016/j.mcpro.2022.100207

APA

Stocks, B., Gonzalez-Franquesa, A., Borg, M. L., Björnholm, M., Niu, L., Zierath, J. R., & Deshmukh, A. S. (2022). Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation. Molecular and Cellular Proteomics, 21(3), [100207]. https://doi.org/10.1016/j.mcpro.2022.100207

Vancouver

Stocks B, Gonzalez-Franquesa A, Borg ML, Björnholm M, Niu L, Zierath JR et al. Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation. Molecular and Cellular Proteomics. 2022;21(3). 100207. https://doi.org/10.1016/j.mcpro.2022.100207

Author

Stocks, Ben ; Gonzalez-Franquesa, Alba ; Borg, Melissa L. ; Björnholm, Marie ; Niu, Lili ; Zierath, Juleen R ; Deshmukh, Atul S. / Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation. In: Molecular and Cellular Proteomics. 2022 ; Vol. 21, No. 3.

Bibtex

@article{12d94e0d847643fa87d8869df454c09d,
title = "Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation",
abstract = "Obesity leads to the development of nonalcoholic fatty liver disease (NAFLD) and associated alterations to the plasma proteome. To elucidate the underlying changes associated with obesity, we performed liquid chromatography-tandem mass spectrometry in the liver and plasma of obese leptin-deficient ob/ob mice and integrated these data with publicly available transcriptomic and proteomic datasets of obesity and metabolic diseases in preclinical and clinical cohorts. We quantified 7173 and 555 proteins in the liver and plasma proteomes, respectively. The abundance of proteins related to fatty acid metabolism were increased, alongside peroxisomal proliferation in ob/ob liver. Putatively secreted proteins and the secretory machinery were also dysregulated in the liver, which was mirrored by a substantial alteration of the plasma proteome. Greater than 50% of the plasma proteins were differentially regulated, including NAFLD biomarkers, lipoproteins, the 20S proteasome, and the complement and coagulation cascades of the immune system. Integration of the liver and plasma proteomes identified proteins that were concomitantly regulated in the liver and plasma in obesity, suggesting that the systemic abundance of these plasma proteins is regulated by secretion from the liver. Many of these proteins are systemically regulated during type 2 diabetes and/or NAFLD in humans, indicating the clinical importance of liver-plasma cross talk and the relevance of our investigations in ob/ob mice. Together, these analyses yield a comprehensive insight into obesity and provide an extensive resource for obesity research in a prevailing model organism.",
author = "Ben Stocks and Alba Gonzalez-Franquesa and Borg, {Melissa L.} and Marie Bj{\"o}rnholm and Lili Niu and Zierath, {Juleen R} and Deshmukh, {Atul S}",
note = "Copyright {\textcopyright} 2022 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2022",
doi = "10.1016/j.mcpro.2022.100207",
language = "English",
volume = "21",
journal = "Molecular and Cellular Proteomics",
issn = "1535-9476",
publisher = "American Society for Biochemistry and Molecular Biology",
number = "3",

}

RIS

TY - JOUR

T1 - Integrated Liver and Plasma Proteomics in Obese Mice Reveals Complex Metabolic Regulation

AU - Stocks, Ben

AU - Gonzalez-Franquesa, Alba

AU - Borg, Melissa L.

AU - Björnholm, Marie

AU - Niu, Lili

AU - Zierath, Juleen R

AU - Deshmukh, Atul S

N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2022

Y1 - 2022

N2 - Obesity leads to the development of nonalcoholic fatty liver disease (NAFLD) and associated alterations to the plasma proteome. To elucidate the underlying changes associated with obesity, we performed liquid chromatography-tandem mass spectrometry in the liver and plasma of obese leptin-deficient ob/ob mice and integrated these data with publicly available transcriptomic and proteomic datasets of obesity and metabolic diseases in preclinical and clinical cohorts. We quantified 7173 and 555 proteins in the liver and plasma proteomes, respectively. The abundance of proteins related to fatty acid metabolism were increased, alongside peroxisomal proliferation in ob/ob liver. Putatively secreted proteins and the secretory machinery were also dysregulated in the liver, which was mirrored by a substantial alteration of the plasma proteome. Greater than 50% of the plasma proteins were differentially regulated, including NAFLD biomarkers, lipoproteins, the 20S proteasome, and the complement and coagulation cascades of the immune system. Integration of the liver and plasma proteomes identified proteins that were concomitantly regulated in the liver and plasma in obesity, suggesting that the systemic abundance of these plasma proteins is regulated by secretion from the liver. Many of these proteins are systemically regulated during type 2 diabetes and/or NAFLD in humans, indicating the clinical importance of liver-plasma cross talk and the relevance of our investigations in ob/ob mice. Together, these analyses yield a comprehensive insight into obesity and provide an extensive resource for obesity research in a prevailing model organism.

AB - Obesity leads to the development of nonalcoholic fatty liver disease (NAFLD) and associated alterations to the plasma proteome. To elucidate the underlying changes associated with obesity, we performed liquid chromatography-tandem mass spectrometry in the liver and plasma of obese leptin-deficient ob/ob mice and integrated these data with publicly available transcriptomic and proteomic datasets of obesity and metabolic diseases in preclinical and clinical cohorts. We quantified 7173 and 555 proteins in the liver and plasma proteomes, respectively. The abundance of proteins related to fatty acid metabolism were increased, alongside peroxisomal proliferation in ob/ob liver. Putatively secreted proteins and the secretory machinery were also dysregulated in the liver, which was mirrored by a substantial alteration of the plasma proteome. Greater than 50% of the plasma proteins were differentially regulated, including NAFLD biomarkers, lipoproteins, the 20S proteasome, and the complement and coagulation cascades of the immune system. Integration of the liver and plasma proteomes identified proteins that were concomitantly regulated in the liver and plasma in obesity, suggesting that the systemic abundance of these plasma proteins is regulated by secretion from the liver. Many of these proteins are systemically regulated during type 2 diabetes and/or NAFLD in humans, indicating the clinical importance of liver-plasma cross talk and the relevance of our investigations in ob/ob mice. Together, these analyses yield a comprehensive insight into obesity and provide an extensive resource for obesity research in a prevailing model organism.

U2 - 10.1016/j.mcpro.2022.100207

DO - 10.1016/j.mcpro.2022.100207

M3 - Journal article

C2 - 35093608

VL - 21

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

SN - 1535-9476

IS - 3

M1 - 100207

ER -

ID: 300911292