Effects of fenofibrate and insulin on the biosynthesis of unsaturated fatty acids in streptozotocin diabetic rats.
Both insulin and PPAR-alpha up-modulate hepatic Delta9, Delta6 and Delta5 desaturating enzymes involved in the biosynthesis of mono- and polyunsaturated fatty acids. Currently, we have examined for 9 days the independent and simultaneous effects of daily glargine insulin and fenofibrate administration on the insulinemia, glycemia, hepatic acyl-CoA oxidase activity and mRNAs and enzymatic activities of stearoyl-CoA desaturase-1 (SCD-1) and Delta5 desaturase in streptozotocin diabetic rats. Glargine insulin depressed the hyperglycemia of diabetic rats at 4h, but not after 24h of injection. Fenofibrate increased the radioimmunoreactive insulinemia in non-diabetic rats without changing the glycemia. Insulin increased the mRNAs and activities of SCD-1 and Delta5 desaturase depressed in diabetic rats. Fenofibrate increased acyl-CoA oxidase activity, and the mRNAs and activities of both desaturating enzymes in non-diabetic, diabetic and insulin-treated diabetic rats, but was less effective in the mRNAs modification of diabetic animals. Therefore, insulin, and fenofibrate through PPAR-alpha activation, enhance liver mRNAs and activities of SCD-1 and Delta5 desaturases independently and synergistically through different mechanisms. Insulin and fenofibrate independently increased the 18:1/18:0 ratio in liver lipids, increasing the fluidity of the membranes. The 20:4/18:2 ratio was maintained. Fenofibrate increased palmitic acid, but decreased stearic acid percentage in liver lipids.
Montanaro
Mauro A
MA
Facultad de Ciencias Médicas,Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, calles 60 y 120, Argentina.
Bernasconi
Ana M
AM
González
Marìa S
MS
Rimoldi
Omar J
OJ
Brenner
Rodolfo R
RR
D042962:Acyl-CoA Oxidase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D000090943:Delta-5 Fatty Acid Desaturase; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000139:chemically induced / Q000201:enzymology; D004195:Disease Models, Animal; D044943:Fatty Acid Desaturases / Q000187:drug effects / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D011345:Fenofibrate / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood*; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase / Q000187:drug effects / Q000378:metabolism; D013311:Streptozocin
D001786:Blood Glucose; D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D008055:Lipids; D012333:RNA, Messenger; D013311:Streptozocin; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; D042962:Acyl-CoA Oxidase; D011345:Fenofibrate