Medium-chain dicarboxylic acylcarnitines as markers of n-3 PUFA-induced peroxisomal oxidation of fatty acids.
METHODS
Omega-3 polyunsaturated fatty acids (n-3 PUFA) found in fish oil activate PPAR-α, stimulate peroxisomal fatty acid (FA) β-oxidation and prevent impairments on glucose homeostasis.


RESULTS
Glucose metabolism and FA oxidation were studied in C57/Bl6 mice fed with diets containing either 3.6 and 31.5% fish oil or lard. To assess the effects of peroxisomal proliferation on FA oxidation independent of n-3 PUFA intake, mice were treated with the PPAR-α agonist WY-14643. n-3 PUFA-fed mice were protected from glucose intolerance and dyslipidemia compared to animals fed a lard-based high-fat diet. Most importantly, mice fed on the hyperlipidic diet based on fish oil as well as the WY-14643 treated mice showed twofold increase of odd, medium-chain, dicarboxylic acylcarnitines in the liver suggesting that not only β-oxidation, but also α- and ω-oxidation of FA were increased. Finally, an oxidation assay using liver homogenates and palmitic acid as substrate revealed an over tenfold increased production of similar acylcarnitines, indicating that FA are their precursors.


CONCLUSIONS
This study shows at the metabolite level that peroxisome proliferation induced either by fish oil or WY-14643 is associated with increased α- and ω-oxidation of FA producing specific acylcarnitines that can be utilized as biomarkers of peroxisomal FA oxidation.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Jarlei
J
Fiamoncini
Emergency Medicine Division, LIM 51-Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.
Thais M
TM
Lima
Institute of Physical Activity and Sports Science, Cruzeiro do Sul University, São Paulo, SP, Brazil.
Sandro M
SM
Hirabara
Biochemistry Unit.
Josef
J
Ecker
Institute of Physical Activity and Sports Science, Cruzeiro do Sul University, São Paulo, SP, Brazil.
Renata
R
Gorjão
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Talita
T
Romanatto
National Research Center, Cairo, Egypt.
Ahmed
A
ELolimy
Clinical Cooperation Group Nutrigenomics and Type 2 Diabetes, Technische Universität München (TUM) and Helmholtz Zentrum München (HMGU), Freising-Weihenstephan and Neuherberg, Germany.
Stefanie
S
Worsch
Clinical Cooperation Group Nutrigenomics and Type 2 Diabetes, Technische Universität München (TUM) and Helmholtz Zentrum München (HMGU), Freising-Weihenstephan and Neuherberg, Germany.
Helmut
H
Laumen
Clinical Cooperation Group Nutrigenomics and Type 2 Diabetes, Technische Universität München (TUM) and Helmholtz Zentrum München (HMGU), Freising-Weihenstephan and Neuherberg, Germany.
Bernhard
B
Bader
Biochemistry Unit.
Hannelore
H
Daniel
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Rui
R
Curi
D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects; D004042:Dietary Fats, Unsaturated / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000627:therapeutic use; D005395:Fish Oils / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D018149:Glucose Intolerance / Q000209:etiology / Q000517:prevention & control; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D050177:Overweight / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D010084:Oxidation-Reduction; D020025:Peroxisome Proliferators / Q000494:pharmacology; D020675:Peroxisomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology
D015415:Biomarkers; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D020025:Peroxisome Proliferators; D011743:Pyrimidines; C116917:acylcarnitine; C006253:pirinixic acid; D002331:Carnitine; C029310:lard
Alpha-oxidation; Beta-oxidation; Omega-3 fatty acids; Omega-oxidation; Peroxisomes