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The hypotriglyceridemic effect of dietary n−3 FA is associated with increased β-oxidation and reduced leptin expression

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Lipids

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 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.

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Abbreviations

AOX:

acyl-CoA oxidase

CPT-1/-2:

carnitine palmitoyltransferase-1 and-2

EHC:

euglycemic hyperinsulinemic clamp

DHA:

docosahexaenoic acid

EPA:

elcosapentaenoic acid

FA:

fatty acid

G3PDH:

glyceraldehyde 3 phosphate dehydrogenase

HDT:

β-oxidation multienzyme complex composed of 2-enoyl-acyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-oxoacyl-CoA thiolase

HF:

high-fat

HF/n−3:

n−3 PUFA-supplemented HF diet

PUFA:

polyunsaturated FA

RT:

reverse transcription

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Author notes

  1. J. Ukropec

    Present address: Pennington Biomedical Research Center, 6400 Perkins Rd., 70808, Baton Rouge, LA

Authors and Affiliations

  1. Institute of Experimental Endocrinology, Diabetes and Nutrition Research Laboratory, Slovak Academy of Sciences, 833 06, Bratislava, Slovak Republic

    J. Ukropec, D. Gasperikova, E. Demcakova, I. Klimes & E. Sebökova

  2. Department of Pharmacology, School of Pharmacy, University of Oslo, 0316, Oslo, Norway

    A. C. Rustan

  3. Department of Clinical Biochemistry, University of Bergen, Haukeland Hospital, Bergen, Norway

    L. Madsen & R. K. Berge

  4. Institute for Nutrition Research, School of Medicine, University of Oslo, P.O. Box 1046 Blindern, 0316, Oslo, Norway

    J. E. Reseland & C. A. Drevon

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  1. J. Ukropec
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  2. J. E. Reseland
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Correspondence to C. A. Drevon.

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Ukropec, J., Reseland, J.E., Gasperikova, D. et al. The hypotriglyceridemic effect of dietary n−3 FA is associated with increased β-oxidation and reduced leptin expression. Lipids 38, 1023–1029 (2003). https://doi.org/10.1007/s11745-006-1156-z

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  • DOI: https://doi.org/10.1007/s11745-006-1156-z

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