Early pro-inflammatory remodeling of HDL proteome in a model of diet-induced obesity: 2H2O-metabolic labeling-based kinetic approach.

Early pro-inflammatory remodeling of HDL proteome in a model of diet-induced obesity: 2H2O-metabolic labeling-based kinetic approach.

Sadana P;Lin Li;Aghayev M;Ilchenko S;Kasumov T

International Journal of Molecular Sciences

2020

2020-10-10

Mice fed a high-fat diet for 12 weeks or longer develop hyperglycemia, insulin resistance, dyslipidemia, and fatty liver. Additionally, a high-fat diet induces inflammation that remodels and affects the anti-inflammatory and antiatherogenic property of the high-density lipoprotein (HDL). However, the precise time course of metabolic disease progression and HDL remodeling remains unclear. Short-term (four weeks) high-fat feeding (60% fat calories) was performed in wild-type male C57BL/6J mice to gain insights into the early metabolic disease processes in conjunction with a HDL proteome dynamics analysis using a heavy water metabolic labeling approach. The high-fat diet-fed mice developed hyperglycemia, impaired glucose tolerance, hypercholesterolemia without hypertriglyceridemia or hepatic steatosis. A plasma HDL proteome dynamics analysis revealed increased turnover rates (and reduced half-lives) of several acute-phase response proteins involved in innate immunity, including complement C3 (12.77 ± 0.81 vs. 9.98 ± 1.20 h, p < 0.005), complement factor B (12.71 ± 1.01 vs. 10.85 ± 1.04 h, p < 0.05), complement Factor H (19.60 ± 1.84 vs. 16.80 ± 1.58 h, p < 0.05), and complement factor I (25.25 ± 1.29 vs. 19.88 ± 1.50 h, p < 0.005). Our findings suggest that an early immune response-induced inflammatory remodeling of the plasma HDL proteome precedes the diet-induced steatosis and dyslipidemia.

inflammation; NAFLD; proteome dynamics; dyslipidemia; insulin resistance; diet-induced obesity; acute-phase proteins; high-density lipoprotein; high-fat diet

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NEOMED College of Pharmacy

NEOMED College of Graduate Studies

Department of Pharmacy Practice

Department of Pharmaceutical Sciences

October 2020 List