Hepatic Lipogenesis and Brain Fatty Acid Profile in Response to Different Dietary n6/n3 Ratios and DHA/EPA Supplementation in Streptozotocin Treated Rats

Abstract

Scope: We investigated the interaction between streptozotocin (STZ)-induced diabetes and dietary n6/n3 ratio, and its influence on lipogenesis.

Methods and results: The animals were treated with STZ and fed with different dietary n6/n3 ratios: 1, 7, and 60, or supplemented with DHA/EPA. Gene expression was assessed by RT-PCR and protein expression by western blotting and immunohistochemistry. Fatty acid profile was determined by GC-MS. Pancreas and liver histology were assessed by hematoxylin and eosin (H&E) staining. STZ-induced characteristic changes in all STZ treated groups, including: increased blood glucose, decreased body mass, increased lipid peroxidation and CD36 expression, decreased 16:1n7 and 18:1n7, increases in 20:3n6, decreases in phospholipid (PL) content of 20:4n6, as well as decreases in the expression of SREBP1c, Δ-9-desaturase (Δ9D), and Δ-5-desaturase (Δ5D). Additionally, other changes occurred that were dependent on the n6/n3 ratio. Among the diabetic groups, the lower n6/n3 ratio caused higher lipid peroxidation and CD36 expression, a greater decrease in 20:4n6 and decreased Δ6-desaturase (Δ6D) expression, while the higher n6/n3 ratio caused increased partitioning of 20:4n6 into hepatic neutral lipids (NL), a decrease in 20:5n3 content, and increased β-oxidation.

Conclusion: Presented data suggest that the n6/n3 ratio could significantly influence lipogenesis, lipid peroxidation, and β-oxidation in STZ-induced diabetes, which could have clinical significance.

Keywords: RAGE; delta-desaturases; diabetes type 1; fatty acids; lipid oxidation; β-oxidation.