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

We studied the long-term influence of gestational diabetes mellitus (GDM) on the pancreas of offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on offspring's pancreas. GDM offspring were divided into three groups: GDM offspring, n-3 PUFA-adequate-GDM offspring, and n-3 PUFA-deficient GDM offspring. All healthy and GDM offspring were fed up to 11 months old. The pancreas of GDM offspring exhibited fatty infiltration at 11 months old, whereas n-3 PUFA improved the pancreatic fatty infiltration. n-3 PUFA lowered the pancreatic oxidative stress and inflammation. Surprisingly, n-3 PUFA postponed pancreatic telomere shortening of GDM offspring at old age. Nontargeted metabolomics showed that many metabolites were altered in the pancreas of GDM offspring at old age, including l-valine, ceramide, acylcarnitines, tocotrienol, cholesteryl acetate, and biotin. n-3 PUFA modulated some altered metabolites and metabolic pathways. Therefore, GDM caused the long-term effects on offspring's pancreas, whereas n-3 PUFA played a beneficial role.

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.

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.

Changes in the metabolite profile of breast milk over lactation stages and their relationship with dietary intake in Chinese women: HPLC-QTOFMS based metabolomic analysis.

The aim of the present study was to comprehensively evaluate the changes in the metabolite profile of breast milk over lactation stages and their relationship with dietary intake in Chinese women by HPLC-QTOFMS based metabolomic analysis. The colostrum, transitional milk and mature milk of thirty healthy lactating women were collected for analysis. Eighty-four differential metabolites over lactation stages were identified, including 12 fatty acyls, 15 glycerolipids, 23 glycerophospholipids, 7 sphingolipids, 7 vitamins, 5 nucleotides-related metabolites, 2 amino acids, 1 amino acid derivate, 9 dipeptides, 1 steroid hormone, 1 energy-related metabolite and 1 amine. Partial least-squares regression analysis indicated that the metabolite profiles of the colostrum, transitional milk and mature milk have a strong relationship with dietary intake (R2 values were 0.92, 0.87 and 0.74, respectively). However, among the 84 differential metabolites over lactation stages, only two showed a strong relationship with dietary intake: 1,24,25-(OH)3 vitamin D3 was positively correlated with the dietary intake of meat and eggs, protein and fat; 11ß-hydroxyprogesterone was negatively correlated with the dietary intake of fruit and carbohydrate. After adjusting for dietary intake, the variation trend of all the 84 differential metabolites over lactation stages remained unchanged. In conclusion, 84 differential metabolites in the breast milk of Chinese women over lactation stages were identified, and their variation trend was independent of dietary intake. These metabolites were partially different from those identified in previous metabolomic studies in the Western population. The present study is quite meaningful for understanding the variation of nutritional requirements in Chinese infants at different developmental stages and manufacturing optimal infant formulas for them.

Retinol and α-tocopherol in human milk and their relationship with dietary intake during lactation.

Human milk is considered as an optimal nutrition source for neonates, and vitamins A and E improve oxidative stress in offspring through breast milk. We aim to determine α-tocopherol and retinol contents in breast milk obtained over the course of lactation stages from mothers in three regions in China, and to investigate their correlation with maternal dietary intake during lactation. Human milk samples and 24 hour food records were obtained from mothers in Hangzhou (n = 34), Lanzhou (n = 34) and Beijing (n = 34) on day 1 (colostrum), day 14 (transitional milk) and day 42 (mature milk) postpartum. Concentrations of α-tocopherol and retinol in breast milk samples were measured by high-performance liquid chromatography. The breast milk concentrations of α-tocopherol and retinol decreased over progress of lactation stages (P < 0.001). The retinol content of transitional milk from Hangzhou was higher than that in Lanzhou (P = 0.019) and Beijing (P < 0.001), and the α-tocopherol content in colostrum from Hangzhou showed a lower concentration than that from Lanzhou (P = 0.001). There was a significantly positive correlation between retinol and α-tocopherol contents in colostrum (r = 0.37, P = 0.002), transitional (r = 0.41, P < 0.001) and mature milk (r = 0.53, P < 0.001). No significant correlation was found between any dietary constituents (grain, fruit, vegetable, dairy, egg and meat, oil and bean products) and either retinol or α-tocopherol.

Short-term toxicity assessments of an antibiotic metabolite in Wistar rats and its metabonomics analysis by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

4-Epi-oxytetracycline (4-EOTC), one of main oxytetracycline (OTC) metabolites, can be commonly detected in food and environment. The toxicity and effects of OTC on animals have been well characterized; however, its metabolites have never been studied systemically. This study aims to investigate 15-day oral dose toxicity and urine metabonomics changes of 4-EOTC after repeated administration in Wistar rats at daily doses of 0.5, 5.0 and 50.0mg/kg bw (bodyweight). Hematology and clinical chemistry parameters, including white blood cell count, red blood cell count, total protein, globulin and albumin/globulin, were obviously altered in rats of 5.0 and 50.0mg/kg bw. Histopathology changes of kidney and liver tissues were also observed in high-dose groups. Urinary metabolites from all groups were analyzed using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Seventeen metabolites contributing to the clusters were identified as potential biomarkers from multivariate analysis, including aminoadipic acid, 6-phosphogluconate, sebacic acid, pipecolic acid, etc. The significant changes of these biomarkers demonstrated metabonomic variations in treated rats, especially lysine and purine metabolism. For the first time in this paper, we combined the results of toxicity and metabonomics induced by 4-EOTC for the serious reconsideration of the safety and potential risks of antibiotics and its degradation metabolites.