Paraoxonase 1 (PON1) and pomegranate influence circadian gene expression and period length.

The circadian timing system regulates key aspects of mammalian physiology. Here, we analyzed the effect of the endogenous antioxidant paraoxonase 1 (PON1), a high-density lipoprotein-associated lipolactonase that hydrolyses lipid peroxides and attenuates atherogenesis, on circadian gene expression in C57BL/6J and PON1KO mice fed a normal chow diet or a high-fat diet (HFD). Expression levels of core-clock transcripts Nr1d1, Per2, Cry2 and Bmal1 were altered in skeletal muscle in PON1-deficient mice in response to HFD.

Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State.

Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis.

Metformin inhibits macrophage cholesterol biosynthesis rate: possible role for metformin-induced oxidative stress.

The aim of the present study was to analyze the metformin (MF) effect on two cellular atherogenic activities: cholesterol biosynthesis and oxidative-stress (OS) as studied in J774A.1 macrophage cell line. MF (2-5 mM) significantly and dose-dependently reduced macrophage cholesterol content and cholesterol biosynthesis rate from acetate, but not from mevalonate, by up to 68% and 71%, respectively.

Paraoxonase1 (PON1) reduces insulin resistance in mice fed a high-fat diet, and promotes GLUT4 overexpression in myocytes, via the IRS-1/Akt pathway.

Objective: To analyze Paraoxonase1 (PON1) impact on GLUT4 expression, glucose metabolism, and the insulin signaling pathway in skeletal muscle cells.

Methods And Results: We analyzed the effect of PON1 in high-fat-diet-induced insulin resistance in C57BL/6J and in PON1KO mice. Mice were fed normal diet (ND) or high Fat Diet (HFD) for 8 weeks.

The antioxidant HDL-associated paraoxonase-1 (PON1) attenuates diabetes development and stimulates β-cell insulin release.

Objective: To analyze the direct effects of paraoxonase-1 (PON1) on diabetes development and on β-cell insulin release.

Methods And Results: Injection of rePON1 to mice, prior to STZ-induced diabetes, resulted in reduced incidence of diabetes, as well as, in higher serum insulin levels. Incubation of β-cells with PON1 also dose-dependently increased insulin secretion and its cellular content.