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The hypotriglyceridemic effect of dietary n−3 FA is associated with increased β‐oxidation and reduced leptin expression
Author(s) -
Ukropec J.,
Reseland J. E.,
Gasperikova D.,
Demcakova E.,
Madsen L.,
Berge R. K.,
Rustan A. C.,
Klimes I.,
Drevon C. A.,
Sebökova E.
Publication year - 2003
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-006-1156-z
Subject(s) - medicine , endocrinology , leptin , carnitine , peroxisome , carnitine palmitoyltransferase i , chemistry , polyunsaturated fatty acid , adipose tissue , beta oxidation , skeletal muscle , biology , metabolism , fatty acid , receptor , biochemistry , obesity
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 β‐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.