Lower Serum Paraoxonase-1 Activity Is Related to Higher Serum Amyloid A Levels in Metabolic Syndrome

Abstract

High-density lipoproteins (HDL) contain the anti-oxidative enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may impair PON-1 activity, whereas SAA and PON-1 are reciprocally regulated in response to acute inflammatory stimuli. The relationship of serum PON-1 activity with SAA during low-grade chronic inflammation is unclear. Here we tested the extent to which low serum PON-1 activity is related to high SAA levels in subjects with and without metabolic syndrome (MetS). In 19 nondiabetic subjects with MetS and 67 subjects without MetS, serum PON-1, assayed as its arylesterase activity, and SAA were measured together with plasma lipids and lipoproteins, high-sensitive C-reactive protein (hs-CRP) and insulin resistance (homeostasis model assessment (HOMA(ir)). PON-1 activity was decreased (p=0.023), whereas SAA levels were increased (p=0.042) in MetS subjects, coinciding with higher hs-CRP levels and HOMA(ir) values. Multiple linear regression analysis revealed that age- and gender-adjusted PON-1 activity was related inversely to SAA (β=-0.256, p=0.020) after adjustment for MetS, or alternatively for hs-CRP and HOMA(ir) (β=-0.271, p=0.049). Decreased serum PON-1 activity in MetS may in part be attributable to higher SAA levels. We suggest that higher SAA levels contribute to impaired HDL anti-oxidative function in MetS via an effect on PON-1 regulation.