Fenofibrate Reduces Age-related Hypercholesterolemia in Normal Rats on a Standard Diet.
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 alpha), 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.
Han
Ying
Y
Department of Pharmacology, Dong-A University College of Medicine, Medical Science Research Center, Busan 602-714, Korea.
Do
Mi-Hyang
MH
Kim
Mi Sun
MS
Seo
Eunhui
E
Park
Mi-Kyoung
MK
Kim
Duk Kyu
DK
Lee
Hye-Jeong
HJ
Seo
Su-Yeong
SY
J Toxicol Sci. 2009 Oct;34(4):377-87
19652460
Exp Gerontol. 2010 Feb;45(2):119-28
19895880
Arch Intern Med. 1999 Aug 9-23;159(15):1670-8
10448768
N Engl J Med. 1995 Feb 23;332(8):512-21
7830734
Curr Opin Chem Biol. 1997 Aug;1(2):235-41
9667857
J Clin Endocrinol Metab. 2004 Feb;89(2):463-78
14764748
Nature. 1990 Oct 18;347(6294):645-50
2129546
Biochem Biophys Res Commun. 2002 Aug 16;296(2):293-9
12163016
Biochem Biophys Res Commun. 2010 Mar 26;394(1):70-4
20171169
FEBS Lett. 2001 Feb 23;491(1-2):154-8
11226439
J Cell Biochem. 2006 Aug 1;98(5):1044-53
16741953
Heart Dis Stroke. 1992 Nov-Dec;1(6):357-65
1344132
J Intern Med. 1997 Oct;242(4):329-37
9366812
Diabetes Metab. 2000 May;26(3):184-91
10880891
Atherosclerosis. 2007 Jul;193(1):112-20
16979646
J Clin Invest. 1991 Feb;87(2):591-6
1991842
Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H1-9
12623780
Kardiol Pol. 2004 Jun;60(6):567-77
15334157
Biochem Biophys Res Commun. 2000 May 10;271(2):445-50
10799317
Clin Ther. 2002 Dec;24(12):2022-50
12581543