Proteome Dynamics Reveals Pro-inflammatory Remodeling Of Plasma Proteome In A Mouse Model Of Nafld

Title

Proteome Dynamics Reveals Pro-inflammatory Remodeling Of Plasma Proteome In A Mouse Model Of Nafld

Creator

Li L; Bebek G; Previs S F; Smith J D; Sadygov R G; McCullough A J; Willard B; Kasumov T

Publisher

Journal of Proteome Research

Date

2016
2016-09

Description

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. Because the liver is the major source of circulatory proteins, it is not surprising that hepatic disease could lead to alterations in the plasma proteome, which are therein implicated in atherosclerosis. The current study used low-density lipoprotein receptor-deficient (LDLR-/-) mice to examine the impact of Western diet (WD)-induced NAFLD on plasma proteome homeostasis. Using a (H2O)-H-2-metabolic labeling method, we found that a WD led to a proinflammatory distribution of circulatory proteins analyzed in apoB-depleted plasma, which was attributed to an increased production. The fractional turnover rates of short-lived proteins that are implicated in stress-response, lipid metabolism, and transport functions were significantly increased with WD (P < 0.05). Pathway analyses revealed that alterations in plasma proteome dynamics were related to the suppression of hepatic PPAR alpha, which was confirmed based on reduced gene and protein expression of PPAR alpha in mice fed a WD. These changes were associated with similar to 4-fold increase (P < 0.0001) in the proinflammatory property of apoB-depleted plasma. In conclusion, the proteome dynamics method reveals proinflammatory remodeling of the plasma proteome relevant to liver disease. The approach used herein may provide a useful metric of in vivo liver function and better enable studies of novel therapies surrounding NAFLD and other diseases.

Subject

antiinflammatory properties; Atherosclerosis; Biochemistry & Molecular Biology; fatty liver-disease; gene-expression; HDL; heavy water; high-density-lipoprotein; mass-spectrometry; NAFLD; oxidized phospholipids; ppar-alpha; proteome dynamics; proteomics; rapid method; shotgun; statistical-model

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

3388-3404

Issue

9

Volume

15

Citation

Li L; Bebek G; Previs S F; Smith J D; Sadygov R G; McCullough A J; Willard B; Kasumov T, “Proteome Dynamics Reveals Pro-inflammatory Remodeling Of Plasma Proteome In A Mouse Model Of Nafld,” NEOMED Bibliography Database, accessed June 15, 2021, https://neomed.omeka.net/items/show/10724.

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