The biosynthesis of DHA is increased in the liver of diabetic rats induced by high‐fat diets and STZ, in correlation with increased activity of peroxisomal β‐oxidation

Abstract

Docosahexaenoic acid (DHA) biosynthesis in the liver is the most important source of extra‐hepatic tissue DHA. However, the levels of DHA and DHA biosynthesis in the livers of animals with type 2 diabetes mellitus remain unknown. In the current study, we used type 2 diabetic rats induced by high‐fat diets and low‐dose streptozotocin (STZ, 25 mg/kg) to investigate DHA biosynthesis in the liver during type 2 diabetes mellitus. The serum and livers were collected. Biochemical characteristics, fatty acid profiles, the activity of peroxisomal β‐oxidation, and the expressions of enzymes involved in the DHA biosynthesis pathway were assayed in the liver of diabetic rats. The data showed that DHA levels were unexpectedly increased despite of the lower expressions of key enzymes, Δ5‐ and Δ6‐desaturases (Δ5D and Δ6D) in the endoplasmic reticulum (ER). The increased DHA was accompanied by an increase in the expression of straight‐chain acyl‐CoA oxidase (SCOX), D‐bifunctional protein (DBP), and 3‐oxoacyl‐CoA thiolase (THL), as well as elevated activity of peroxisomal β‐oxidation and an increased capacity for DHA biosynthesis from C24:6n‐3. These findings indicate that DHA biosynthesis is increased in the livers of diabetic rats induced by high‐fat diets and STZ, and that this effect is related to increased activity of peroxisomal β‐oxidation, but not of ER desaturases.Practical applications: The results support the hypothesis that the dietary supplementation in diabetes with DHA and EPA is desirable.The pathway of DHA biosynthesis in the liver of rats induced by high‐fat diets and STZ is shown. DHA biosynthesis is increased in the livers of diabetic rats induced by high‐fat diets and STZ, and this effect is related to increased activity of peroxisomal β‐oxidation, but is not related to the activity of ER desaturases.