Vascular and metabolic profiles in offspring born to pregnant mice with metabolic syndrome treated with inositols

Abstract

BACKGROUND: Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOSþ/e) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype. OBJECTIVE: Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS. MATERIALS AND METHODS: Heterozygous eNOSþ/e mice fed an HFD manifest a MS phenotype. Female eNOSþ/e mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/ DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOSþ/e offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9e10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed. RESULTS: The GTT showed lower glucose levels in both eNOSþ/eINOs (P ¼ .03) and WT-INOs (P ¼ .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOSþ/e offspring compared to WT (169 AE 7 vs 142 AE 9 mm Hg, respectively, P ¼ .04) and INOs treatment decreased SBP in WT-INOs (110 AE 10 mm Hg, P ¼ .01) but not in eNOSþ/eINOs offspring. Maximal (%Max) contractile response to PE was higher in eNOSþ/e offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOSþ/e, 123 AE 7 vs eNOSþ/eINOs, 82 AE 11 mm Hg, P ¼ .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 AE 4 vs WT-INOs, 75 AE 7). The L-NAME response was decreased in eNOSþ/e INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOSþ/e and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P ¼ .01 and P ¼ .03, respectively). No differences were seen in response to SNP. CONCLUSION: Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOSþ/e and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOSþ/e offspring ...

Immune status, and not HIV infection or exposure, drives the development of the oral microbiota

“…Nevertheless, differences in oral microbiota between HEU and HUU children have not been previously reported. By suppressing immune function, perinatal HIV exposure and/or infection could disrupt development of the oral microbiota and drive biological functions related to HIV progression in HI infants and poorer development outcomes in HEU children 33 .…”

“…dren were enrolled for this study for comparison;-HI, HEU, and HUU children. Mother-child dyads were recruited from specific UBTH clinics as previously described 33 . Briefly, HI and HEU children were recruited from the HIV/AIDS pediatric clinic or based on referral by mothers attending the adult ART clinic at UBTH.…”

Maternal N-Acetyl Cysteine Intake Improved Glucose Tolerance in Obese Mice Offspring

“…Characterizing specific deleterious in-utero environmental factors and developing strategies to eliminate their exposure might lead to breaking this negative cycle of inheritance. In addition, several dietary ingredients supplemented in-utero and during the lactation period (i.e., resveratrol, omega-3 fatty acids and inositols [36][37][38][39]) were found to partially prevent adverse outcomes of poor maternal diet in the adult offspring. One mechanism suggested to mediate the benefits of some of these supplements was by negating diet-induced oxidative stress.…”

An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs)

“…From the experimental point of view, recent animal studies showed that combined inositols treatment (MI/DCI 40:1) in pregnant mouse complicated by metabolic syndrome and obesity improved blood pressure, glucose levels at the glucose tolerance, as well as leptin levels [70]. In addition, the same combination of inositols treatment improved not only maternal outcomes, but also offspring weight at birth as well as glucose tolerance test, and vascular reactivity in their adult life, thus reducing the vicious cycle of dysmetabolism [71]. Finally, it should be highlighted that inositols administration in pregnancy was well tolerated and found to be safe, unlike metformin which has been associated with several gastrointestinal symptoms [63].…”