Reduction of n-3 PUFAs, specifically DHA and EPA, and enhancement of peroxisomal beta-oxidation in type 2 diabetic rat heart.
BACKGROUND
There is overwhelming evidence that dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs), mainly EPA (C20:5n-3) and DHA (C22:6n-3), has cardiovascular protective effects on patients with type 2 diabetes mellitus (T2DM) but not on healthy people. Because the T2DM heart increases fatty acid oxidation (FAO) to compensate for the diminished utilization of glucose, we hypothesize that T2DM hearts consume more n-3 PUFAs and, therefore, need more n-3 PUFAs. In the present study, we investigated the changes in cardiac n-3 PUFAs and peroxisomal beta-oxidation, which are responsible for the degradation of PUFAs in a high-fat diet (HFD) and low-dose streptozotocin- (STZ) induced type 2 diabetic rat model.


RESULTS
The capillary gas chromatography results showed that all the n-3 (or omega-3) PUFAs, especially DHA (~50%) and EPA (~100%), were significantly decreased, and the n-6/n-3 ratio (~115%) was significantly increased in the hearts of diabetic rats. The activity of peroxisomal beta-oxidation, which is crucial to very-long-chain and unsaturated FA metabolism (including DHA), was significantly elevated in DM hearts. Additionally, the real-time PCR results showed that the mRNA expression of most peroxisomal beta-oxidation key enzymes were up-regulated in T2DM rat hearts, which might contribute to the reduction of n-3 (or omega-3) PUFAs.


CONCLUSIONS
In conclusion, our results indicate that T2DM hearts consume more n-3 PUFAs, especially DHA and EPA, due to exaggerated peroxisomal beta-oxidation.
Department of Biochemistry and Molecular Biology, The Key Laboratory of Neurobiology and Vascular Biology, China Administration of Education, Hebei Medical University, No, 361 Zhongshan East Road, Shijiazhuang, 050017, China.
Lianguo
L
Hou
Kaoqi
K
Lian
Min
M
Yao
Yun
Y
Shi
Xin
X
Lu
Lijia
L
Fang
Tianbo
T
He
Lingling
L
Jiang
D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002849:Chromatography, Gas; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000097:blood / Q000378:metabolism*; D004734:Energy Metabolism; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C576488:Acox3 protein, rat; D042962:Acyl-CoA Oxidase