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Abstract
Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR α), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.
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Fig. 1.
(A) Effect of fenofibrate on daily food intake. There was no significant change in daily food intake from 10 to 25 weeks of age. There was no significant difference in daily food intake between the fenofibrate and control groups at 25 weeks of age. (B) Effect of fenofibrate on body weight. Body weight of SD rats increased with age. There was no significant difference in body weight between fenofibrate and control groups at 25 weeks of age. Values represent means±SEM of the control group (n=7) and the fenofibrate group (n=8). Feno, fenofibrate; Tx, treatment.
Fig. 2.
Analysis of blood glucose levels. (A) Effect of fenofibrate on fasting blood glucose. There was no significant change in fasting blood glucose from 10 to 25 weeks of age. There was no significant difference in fasting blood glucose between the fenofibrate and control groups at 25 weeks of age. (B) Effect of fenofibrate on random blood glucose levels. There was no significant change in random blood glucose from 10 to 25 weeks of age. There was no significant difference in random blood glucose between the fenofibrate and control groups at 25 weeks of age. Values represent means±SEM of the control group (n=7) and the fenofibrate group (n=8). Feno, fenofibrate; Tx, treatment.
Fig. 3.
Changes in plasma TC, TG, and FFA levels with age. (A) Plasma TC level was significantly increased from 10 to 25 weeks of age. (B) The plasma TG level was not changed from 10 to 25 weeks of age. (C) Plasma FFA levels were significantly increased from 10 to 25 weeks of age. Values represent means±SEM of the SD rats (n=15). ∗p<0.05 vs. 10 weeks of age; ∗∗p<0.01 vs. 10 weeks of age.
Fig. 4.
Effects of fenofibrate on plasma TC, TG, and FFA levels. There was no difference in plasma TC, TG, and FFA levels between the fenofibate and control groups before fenofibrate treatment. (A) After 5 weeks of fenofibrate treatment, the plasma TC level of the fenofibrate group was significantly lower than that of the control group. (B) After 5 weeks of fenofibrate treatment, there was no significant difference in plasma TG level between the fenofibrate and control groups. (C) After 5 weeks of fenofibrate treatment, the plasma FFA level of the fenofibrate group was significantly lower than that of the control group. Values represent means±SEM of the control (n=7) and fenofibrate (n=8) groups. ∗p<0.05 vs. control group.
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