Effects of fenofibrate and insulin on the biosynthesis of unsaturated fatty acids in streptozotocin diabetic rats

• Published in: Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2005-11, Vol.73 (5), p.369-378
• Main Authors: Montanaro, Mauro A., Bernasconi, Ana M., González, Marìa S., Rimoldi, Omar J., Brenner, Rodolfo R.
• Format: Article
• Language: English
• Subjects: Acyl-CoA Oxidase - drug effects; Acyl-CoA Oxidase - metabolism; Animals; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - enzymology; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Acid Desaturases - drug effects; Fatty Acid Desaturases - metabolism; Fatty Acids, Unsaturated - biosynthesis; Fenofibrate - administration & dosage; Fundamental and applied biological sciences. Psychology; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin - blood; Lipids - chemistry; Liver - chemistry; Liver - enzymology; Liver - metabolism; Male; Medical sciences; Rats; Rats, Wistar; RNA, Messenger - drug effects; Stearoyl-CoA Desaturase - drug effects; Stearoyl-CoA Desaturase - metabolism; Streptozocin; Vertebrates: endocrinology
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2005.06.004

Both insulin and PPAR- α up-modulate hepatic Δ9, Δ6 and Δ5 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 Δ5 desaturase in streptozotocin diabetic rats. Glargine insulin depressed the hyperglycemia of diabetic rats at 4 h, but not after 24 h 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 Δ5 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- α activation, enhance liver mRNAs and activities of SCD-1 and Δ5 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.