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

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease (CVD). Liver is the major source of the circulatory proteins and alterations in plasma proteome have been implicated in atherosclerosis. We used a recently developed 2H2O-metabolic labeling method in combination with the label-free quantification to evaluate the effect of a Western diet (WD) on the dynamics of plasma proteins in LDL receptor-deficient (LDLR-/-) mice, a model of NAFLD and atherosclerosis. There were no significant changes in the expression level of total proteins due to the WD with a bulk protein mean half-life of 18.0±15.1 hours in control and 16.7±11.1 hours in WD groups. WD led to pro-inflammatory distribution of circulatory proteins analyzed in apoB-depleted plasma attributed to their increased production. The fractional catabolic rates of fast-turnover proteins with stress-response, lipid metabolism and transport functions were significantly increased with WD (P<0.05). The 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 on WD. These changes were associated with ~4 fold increase (P<0.0001) in pro-inflammatory property of apoB-depleted plasma. In conclusion, the proteome dynamics method reveals pro-inflammatory remodeling of plasma proteome relevant to liver disease. As in vivo metrics of liver function, this approach can be used to test therapies in NAFLD and other diseases

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Ling Li

LAB HEAD: Ling Li

PROVIDER: PXD004270 | Pride | 2016-06-06

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Kine-SD-0h.dat	Other
	Kine-SD-0h.mgf	Mgf
	Kine-SD-0h.raw	Raw
	Kine-SD-1day.dat	Other
	Kine-SD-1day.mgf	Mgf

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