The online version of this article (doi:10.1186/1475-2840-11-126) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
LGH was the principal investigator, involved in designing the study, performing the quantitative real-time PCR assays and writing the manuscript. KQL carried out and analyzed capillary gas chromatography assays. MY and YS helped to perform statistical analyses and write parts of the manuscript. XL, LJF and TBH participated in experiments in vivo and performed the fatty acid beta-oxidation activity assays. LLJ designed and supervised the study as well as helped to draft the manuscript. All authors read and approved the final manuscript.
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.
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.
In conclusion, our results indicate that T2DM hearts consume more n-3 PUFAs, especially DHA and EPA, due to exaggerated peroxisomal beta-oxidation.
Hu Q, Ishii E, Nakagawa Y: Differential changes in relative levels of arachidonic acid in major phospholipids from rat tissues during the progression of diabetes. J Biochem. 1994, 115 (3): 405-408. PubMed
Vega RB, Huss JM, Kelly DP: The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol. 2000, 20 (5): 1868-1876. 10.1128/MCB.20.5.1868-1876.2000. PubMedCentralCrossRefPubMed
Razny U, Kiec-Wilk B, Wator L, Polus A, Dyduch G, Solnica B, Malecki M, Tomaszewska R, Cooke JP, Dembinska-Kiec A: Increased nitric oxide availability attenuates high fat diet metabolic alterations and gene expression associated with insulin resistance. Cardiovasc Diabetol. 2011, 10: 68-10.1186/1475-2840-10-68. PubMedCentralCrossRefPubMed
Koopmans SJ, Dekker R, Ackermans MT, Sauerwein HP, Serlie MJ, van Beusekom HM, van den Heuvel M, van der Giessen WJ: Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs. Cardiovasc Diabetol. 2011, 10: 64-10.1186/1475-2840-10-64. PubMedCentralCrossRefPubMed
Bilbao E, Cajaraville MP, Cancio I: Cloning and expression pattern of peroxisomal beta-oxidation genes palmitoyl-CoA oxidase, multifunctional protein and 3-ketoacyl-CoA thiolase in mussel Mytilus galloprovincialis and thicklip grey mullet Chelon labrosus. Gene. 2009, 443 (1–2): 132-142. CrossRefPubMed
Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, Fonseca V, Gerstein HC, Grundy S, Nesto RW, Pignone MP, Plutzky J, Porte D, Redberg R, Stitzel KF, Stone NJ, American Heart Association; American Diabetes Association: Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation. 2007, 115 (1): 114-126. CrossRefPubMed
Chicco AJ, Sparagna GC, McCune SA, Johnson CA, Murphy RC, Bolden DA, Rees ML, Gardner RT, Moore RL: Linoleate-rich high-fat diet decreases mortality in hypertensive heart failure rats compared with lard and low-fat diets. Hypertension. 2008, 52 (3): 549-555. 10.1161/HYPERTENSIONAHA.108.114264. PubMedCentralCrossRefPubMed
Lepage G, Roy CC: Specific methylation of plasma nonesterified fatty acids in a one-step reaction. J Lipid Res. 1988, 29 (2): 227-235. PubMed
Vrablik M, Prusikova M, Snejdrlova M, Zlatohlavek L: Omega-3 fatty acids and cardiovascular disease risk: do we understand the relationship?. Physiol Res. 2009, 58 (Suppl 1): S19-S26. PubMed
Buchanan J, Mazumder PK, Hu P, Chakrabarti G, Roberts MW, Yun UJ, Cooksey RC, Litwin SE, Abel ED: Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology. 2005, 146 (12): 5341-5349. 10.1210/en.2005-0938. CrossRefPubMed
Finck BN, Han X, Courtois M, Aimond F, Nerbonne JM, Kovacs A, Gross RW, Kelly DP: A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc Natl Acad Sci U S A. 2003, 100 (3): 1226-1231. 10.1073/pnas.0336724100. PubMedCentralCrossRefPubMed
- Reduction of n-3 PUFAs, specifically DHA and EPA, and enhancement of peroxisomal beta-oxidation in type 2 diabetic rat heart
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