Antidyslipidemic action of fenofibrate in dyslipidemic-diabetic hamster model.
Fenofibrate is the ligand for PPARalpha subtype that mediates the action of its agonists' in lipid metabolism. How fibrate exerts hypolipidemic effect? The mechanism is studied in a newly developed high-fat fructose enriched diet induced dyslipidemia-diabetic hamster model. Fenofibrate lowered the basal plasma lipids like TC, TG, PL, FFA, glycerol, VLDL, and LDL, but HDL was increased. The activity of lipoprotein lipase in liver, adipose tissue, and small intestine was upregulated. However, that of triglyceride lipase was downregulated in liver. It has also improved the insulin secretion and plasma glucose lowering, caused by impairment in insulin secretion due to high-fat load. The drug was found effective in reducing body weight and diet due to rise in leptin level. Fenofibrate also enhanced the fecal excretion of total lipids, cholic acid, and deoxycholic acid probably by the activation of 7alpha cholesterol hydroxylase enzyme. Thus, causing broad-spectrum lipid lowering along with inhibition of hepatic lipid biosynthesis and maintaining lipid-glucose homeostasis.
Division of Biochemistry, Central Drug Research Institute, Lucknow 226001, India. farhanrizvi@rediffmail.com
F
F
Rizvi
A
A
Puri
G
G
Bhatia
A K
AK
Khanna
E M
EM
Wulff
A K
AK
Rastogi
R
R
Chander
D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D006224:Cricetinae; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005223:Fats / Q000008:administration & dosage; D005243:Feces / Q000737:chemistry; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008049:Lipase / Q000378:metabolism; D008055:Lipids / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D014018:Tissue Distribution; D014157:Transcription Factors / Q000819:agonists
D001647:Bile Acids and Salts; D001786:Blood Glucose; D005223:Fats; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D008049:Lipase; D008071:Lipoprotein Lipase; D011345:Fenofibrate