Effects of different DHA and ARA ratios for improving gestational diabetic mellitus in pregnant mice

This study aimed to investigate the effects of docosahexaenoic acid (DHA): arachidonic acid (ARA) on glucose and lipid metabolism and hepatic metabolites in gestational diabetes mellitus (GDM) mice. Experimental groups received different interventions of DHA alone, DHA:ARA of 4:1, 1:1, 1:4, and ARA alone. The DHA:ARA ratios of 1:1 and 1:4 were superior in reducing the blood glucose, total cholesterol, triglyceride, and low-density lipoprotein, alleviating oxidative stress and inflammatory responses, and improving hepatic pathology. Hepatic metabolomics analysis revealed 12 upregulated and 9 downregulated metabolites after 1:1 ratios intervention versus GDM mice, and 11 upregulated and 8 downregulated after 1:4 ratios. For example, the levels of hypotaurine and guanine significantly increased, while L-isoleucine levels decreased in both DHA:ARA = 1:1 and 1:4 groups. DHA:ARA = 1:1 intervention restored allantoin level but downregulated serine level. Thus, abnormal hepatic metabolism associated with GDM was ameliorated. Pathway analysis indicated that DHA:ARA = 1:1 and 1:4 alleviated the GDM by three main metabolic pathways, namely valine, leucine, and isoleucine biosynthesis, taurine and hypotaurine metabolism, and purine metabolism. In conclusion, DHA:ARA ratios of 1:1 and 1:4 significantly improve abnormal glucose and lipid metabolism and hepatic metabolites caused by GDM.