title: The hypotriglyceridemic effect of dietary n-3 FA is associated with increased beta-oxidation and reduced leptin expression.
abstract: To study the mechanisms responsible for the hypotriglyceridemic effect of marine oils, we monitored the effects of high dietary intake of n-3 PUFA on hepatic and muscular beta-oxidation, plasma leptin concentration, leptin receptor gene expression, and in vivo insulin action. Two groups of male Wistar rats were fed either a high-fat diet [28% (w/w) of saturated fat] or a high-fat diet containing 10% n-3 PUFA and 18% saturated fat for 3 wk. The hypotriglyceridemic effect of n-3 PUFA was accompanied by increased hepatic oxidation of palmitoyl-CoA (125%, P < 0.005) and palmitoyl-L-carnitine (480%, P < 0.005). These findings were corroborated by raised carnitine palmitoyltransferase-2 activity (154%, P < 0.001) and mRNA levels (91%, P < 0.01) as well as by simultaneous elevation of hepatic peroxisomal acyl-CoA oxidase activity (144%, P < 0.01) and mRNA content (82%, P < 0.05). In contrast, hepatic carnitine palmitoyltransferase-1 activity remained unchanged despite a twofold increased mRNA level after n-3 PUFA feeding. Skeletal muscle FA oxidation was less affected by dietary n-3 PUFA, and the stimulatory effect was found only in peroxisomes. Dietary intake of n-3 PUFA was followed by increased acyl-CoA oxidase activity (48%, P < 0.05) and mRNA level (83%, P < 0.05) in skeletal muscle. The increased FA oxidation after n-3 PUFA supplementation of the high-fat diet was accompanied by lower plasma leptin concentration (-38%, P < 0.05) and leptin mRNA expression (-66%, P < 0.05) in retroperitoneal adipose tissue, and elevated hepatic mRNA level for the leptin receptor Ob-Ra (140%, P < 0.05). Supplementation of the high-fat diet with n-3 PUFA enhanced in vivo insulin sensitivity, as shown by normalization of the glucose infusion rate during euglycemic hyperinsulinemic clamp. Our results indicate that the hypotriglyceridemic effect of dietary n-3 PUFA is associated with stimulation of FA oxidation in the liver and to a smaller extent in skeletal muscle. This may ameliorate dyslipidemia, tissue lipid accumulation, and insulin action, in spite of decreased plasma leptin level and leptin mRNA in adipose tissue.
authors.affiliation: Institute of Experimental Endocrinology, Diabetes and Nutrition Research Laboratory, Slovak Academy of Sciences, 833 06 Bratislava, Slovak Republic.
authors.forename: J
authors.initials: J
authors.lastname: Ukropec
authors.forename: J E
authors.initials: JE
authors.lastname: Reseland
authors.forename: D
authors.initials: D
authors.lastname: Gasperikova
authors.forename: E
authors.initials: E
authors.lastname: Demcakova
authors.forename: L
authors.initials: L
authors.lastname: Madsen
authors.forename: R K
authors.initials: RK
authors.lastname: Berge
authors.forename: A C
authors.initials: AC
authors.lastname: Rustan
authors.forename: I
authors.initials: I
authors.lastname: Klimes
authors.forename: C A
authors.initials: CA
authors.lastname: Drevon
authors.forename: E
authors.initials: E
authors.lastname: Sebökova
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000097:blood / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D020738:Leptin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000037:antagonists & inhibitors* / Q000097:blood*
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D000960:Hypolipidemic Agents; D020738:Leptin; D014280:Triglycerides