title: The effect of combined inositol supplementation on maternal metabolic profile in pregnancies complicated by metabolic syndrome and obesity.
abstract: Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype.
  
  
  
  The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model.
  
  
  
  Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice.
  
  
  
  Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol-treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity.
  
  
  
  Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas; Department of Obstetrics and Gynecology, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: ferrari196@yahoo.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrari
authors.affiliation: Department of Obstetrics and Gynecology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchinetti
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Alejandra E
authors.initials: AE
authors.lastname: Ontiveros
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Robyn P
authors.initials: RP
authors.lastname: Roberts
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Mia M
authors.initials: MM
authors.lastname: Saade
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Blackwell
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Baha M
authors.initials: BM
authors.lastname: Sibai
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Jerrie S
authors.initials: JS
authors.lastname: Refuerzo
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005865:Gestational Age; D054439:Ghrelin / Q000097:blood; D005951:Glucose Tolerance Test; D007294:Inositol / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D009765:Obesity / Q000097:blood / Q000150:complications*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D007294:Inositol; D005749:Gastric Inhibitory Polypeptide; D052250:Nitric Oxide Synthase Type III
keywords: C57BL/6J mice; blood pressure; endothelial nitric oxide synthase inositol; insulin resistance; knockout mice metabolic syndrome; obesity; pregnancy