Proteome Dynamics Reveals Pro-Inflammatory Remodeling of Plasma Proteome in a Mouse Model of NAFLD

Ling Li, Gurkan Bebek, Stephen F. Previs, Jonathan D. Smith, Rovshan Sadygov, Arthur J. McCullough, Belinda Willard, Takhar Kasumov

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 2H2O-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 PPARα, which was confirmed based on reduced gene and protein expression of PPARα in mice fed a WD. These changes were associated with 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.

Original languageEnglish (US)
Pages (from-to)3388-3404
Number of pages17
JournalJournal of Proteome Research
Volume15
Issue number9
DOIs
StatePublished - Sep 2 2016

Keywords

  • atherosclerosis
  • HDL
  • heavy water
  • NAFLD
  • proteome dynamics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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    Li, L., Bebek, G., Previs, S. F., Smith, J. D., Sadygov, R., McCullough, A. J., Willard, B., & Kasumov, T. (2016). Proteome Dynamics Reveals Pro-Inflammatory Remodeling of Plasma Proteome in a Mouse Model of NAFLD. Journal of Proteome Research, 15(9), 3388-3404. https://doi.org/10.1021/acs.jproteome.6b00601