n-3 Polyunsaturated Fatty Acids Decrease Long-Term Diabetic Risk of Offspring of Gestational Diabetes Rats by Postponing Shortening of Hepatic Telomeres and Modulating Liver Metabolism

Abstract

The long-term influence of gestational diabetes mellitus (GDM) on offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on GDM offspring are poorly understood. We studied the long-term diabetic risk in GDM offspring and evaluated the effect of n-3 PUFA intervention. Healthy offspring rats were fed standard diet (soybean oil) after weaning. GDM offspring were divided into three groups: GDM offspring (soybean oil), n-3 PUFA adequate offspring (fish oil), and n-3 PUFA deficient offspring (safflower oil), fed up to 11 months old. The diabetic risk of GDM offspring gradually increased from no change at weaning to obvious impaired glucose and insulin tolerance at 11 months old. N-3 PUFA decreased oxidative stress and inflammation in the liver of older GDM offspring. There was a differential effect of n-3 PUFA and n-6 PUFA on hepatic telomere length in GDM offspring. Non-targeted metabolomics showed that n-3 PUFA played a modulating role in the liver, in which numerous metabolites and metabolic pathways were altered when GDM offspring grew to old age. Many metabolites were related to diabetes risk, such as α-linolenic acid, palmitic acid, ceramide, oxaloacetic acid, tocotrienol, tetrahydro-11-deoxycortisol, andniacinamide. In summary, GDM offspring exhibited obvious diabetes risk at old age, whereas n-3 PUFA decreased this risk.

Beneficial Effects of n-3 Polyunsaturated Fatty Acids on Offspring’s Pancreas of Gestational Diabetes Rats

“…The protein concentrations were determined through a colorimetric assay. Commercially available kits were used to measure the level of malondialdehyde (MDA) and glutathione (GSH) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) according to the manufacturer’s instructions (Nanjing Jiancheng Biotechnology Institute, Nanjing, China) …”

“…The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 in the pancreas of GDM offspring were determined using commercially available ELISA kits (Nanjing Jiancheng Biotechnology Institute, Nanjing, China) according to the manufacturer’s instructions …”

Functional food ingredients for control of gestational diabetes mellitus: a review

“…GDM is associated with inhibition of glycogen synthesis, affecting the citric acid cycle and gluconeogenesis (Gao et al, 2019b). One study reported that the prevalence of non-alcoholic fatty liver disease among women with a history of GDM was 14-38% higher than in women without such history (Sattari et al, 2020).…”

Immunometabolism in type 2 diabetes mellitus: tissue-specific interactions

“…During obesity, the excess of lipids in the AT promotes lipotoxicity, leading to liver damage and macrophage infiltration [201,202,221]. Again, the dietary composition of lipids may play an important role in this context, with omega-3 FFAs displaying interesting anti-inflammatory properties [222][223][224]. Along with the KC, these macrophages have been indicated as mediators of hepatic inflammation during obesity.…”