**2.1.3 Serum uric acid-reducing actions**

Hyperuricemia, a common co-morbidity in the patients with metabolic syndrome and dyslipidemia has recently been emphasized as an independent risk factor for cardiovascular disease (Lippi et al., 2008).

Kodama et al. performed a meta-analysis of 11 clinical studies, and reported that a 1-mg/dL increase in the serum uric acid level significantly elevated the relative risk of type II DM by 1.17-fold (Kodama et al., 2009). Schretlen et al. investigated 96 persons aged 60 to 92 years, and indicated that the information-processing capacity and memory were reduced in persons with high uric acid level, suggesting that the serum uric acid level may be a prognostic factor for dementia (Schretlen et al., 2007). Thus, hyperuricemia may play a role not only in the onset of cardiovascular disease but also in the promotion of dementia and aging.

Fenofibrate has been known to reduce the serum levels of lipids and also uric acid (Schlesinger et al., 2009). The serum uric acid-reducing action mechanism of fenofibrate, independent of lipid-profile changes, involves the promotion of uric-acid excretion (Liamis et al., 1999).

Urate Transporter 1 (URAT1), the target molecule of uric acid-reducing agents such as benzbromarone was identified which is responsible for the reabsorption of uric acid in the proximal uriniferous tubule (Enomoto et al., 2002). Furthermore, URAT1 inhibition was involved in the serum uric acid-reducing action mechanism of fenofibrate (Uetake et al., 2010). According to their study, the single-dose administration of standard fenofibrate at 300

statins, represented by atorvastatin, also inhibit CoQ10 biosynthesis in vivo, leading to the

The administration of standard fenofibrate at 150 mg/day to 18 Japanese type II DM with dyslipidemia for 12 weeks significantly decreased the triglyceride (TG) level (from 232±109 to 145±74 mg/dL, -37%, p<0.01), and significantly improved the HDL-C level (from 45±8.7

The plasma ubiquinol-10 level in fenofibrate group increased significantly after 8 weeks (from 768±265 to 886±310 nM, p<0.05) and after 12 weeks (from 768±265 to 894±336 nM, p<0.05). However, total plasma CoQ10 level (ubiquinol-10 plus ubiquinone-10) as an oxidative stress marker, decreased in statin group, elevated in fenofibrate group after 12 weeks administration (from 1010±296 to 1070±285 nM, +6%). In addition, plasma ubiquinone-10 in fenofibrate group decreased insignificantly. Fenofibrate treatment elevates

In the wild-type mice administered by diethylhexylphthalate (DEHP: PPAR-α activator), elevation of plasma ubiquinone was significant, but the elevation was not observed in the PPAR-α-null mice (Turunen et al., 2000). In addition, the expression of PPAR-α gene was regulated in the liver of SAMP1 (senescence accelerated mouse prone 1) mice given ubiquinol for long term (Schmelzer et al., 2010a, 2010b). Although the antioxidant action mechanisms of fenofibrate remained unclear in human, mice studies suggested the direct

Fenofibrate not only restores the serum lipid profiles, but also suppresses oxidative stress. Fenofibrate with a variety of pleiotropic activities may protect the pathogenesis and

Hyperuricemia, a common co-morbidity in the patients with metabolic syndrome and dyslipidemia has recently been emphasized as an independent risk factor for cardiovascular

Kodama et al. performed a meta-analysis of 11 clinical studies, and reported that a 1-mg/dL increase in the serum uric acid level significantly elevated the relative risk of type II DM by 1.17-fold (Kodama et al., 2009). Schretlen et al. investigated 96 persons aged 60 to 92 years, and indicated that the information-processing capacity and memory were reduced in persons with high uric acid level, suggesting that the serum uric acid level may be a prognostic factor for dementia (Schretlen et al., 2007). Thus, hyperuricemia may play a role not only in the onset of cardiovascular disease but also in the promotion of dementia and

Fenofibrate has been known to reduce the serum levels of lipids and also uric acid (Schlesinger et al., 2009). The serum uric acid-reducing action mechanism of fenofibrate, independent of lipid-profile changes, involves the promotion of uric-acid excretion (Liamis

Urate Transporter 1 (URAT1), the target molecule of uric acid-reducing agents such as benzbromarone was identified which is responsible for the reabsorption of uric acid in the proximal uriniferous tubule (Enomoto et al., 2002). Furthermore, URAT1 inhibition was involved in the serum uric acid-reducing action mechanism of fenofibrate (Uetake et al., 2010). According to their study, the single-dose administration of standard fenofibrate at 300

increase in oxidative stress (Mabuchi et al., 2005).

to 52±9.8 mg/dL, +14%, p<0.01) (Asano et al., 2006).

plasma CoQ10, especially plasma ubiquinol-10 level.

interaction between CoQ10 and PPAR-α.

**2.1.3 Serum uric acid-reducing actions** 

disease (Lippi et al., 2008).

aging.

et al., 1999).

progression of aging-associated atherosclerosis.
