Reduction of n-3 PUFAs, specifically DHA and EPA, and enhancement of peroxisomal beta-oxidation in type 2 diabetic rat heart

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.Type 2 diabetes mellitus (T2DM) is associated with high cardiovascular morbidity and mortality [1]. In patients with diabetes, the fatty acid (FA) supply to the heart increases to compensate for the diminished utilization of glucose as an energy source. Although the dramatic increase in FA influx markedly increases the fatty acid oxidation (FAO) [2], it also leads to elevated FA and subsequent triglyceride (TG) synthesis in the diabetic heart, causing cellular lipotoxicity and the initiation of cardiac dysfunction [3]. Alternatively, the diabetic heart is characterized by significant alterations in the fatty acid composition of heart membranes. It has been shown that the linoleic acid (C18:2n-6) content is increased [4] and the n-3 polyunsaturated fatty acid (PUFA) content is decreased [5] in the cardiac phospholipids of STZ-treated rats and fructose-fed rats.Fatty acids are degraded by both mitochondrial and peroxisomal β-oxidation. The fatty acids that are shorter than C20 are primarily oxidized in the mitochondria, and the fatty acids that are greater than C22 (very-long-chain fatty acids, VLCFA), including polyunsaturated fatty acids (PUFA, Polyenoic acids with 20–22 carbon atoms and 3–6 double