title: Maternal Hyperleptinemia Is Associated with Male Offspring's Altered Vascular Function and Structure in Mice.
abstract: Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Leprdb/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under a standard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post -natal environments to contribute to altered vascular function in offspring of diabetic pregnancies.
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Pennington
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States of America.|Department of Biological Engineering, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Francisco I
authors.initials: FI
authors.lastname: Ramirez-Perez
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Pollock
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, United States of America.|Division of Biological Sciences, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Omonseigho O
authors.initials: OO
authors.lastname: Talton
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Foote
authors.affiliation: School of Engineering and Mathematical Sciences, City University London, London, United Kingdom.
authors.forename: Constantino C
authors.initials: CC
authors.lastname: Reyes-Aldasoro
authors.affiliation: Department of Statistics, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Ho-Hsiang
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Statistics, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Tieming
authors.initials: T
authors.lastname: Ji
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States of America.|Department of Biological Engineering, University of Missouri, Columbia, Missouri, United States of America.|Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Martinez-Lemus
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, United States of America.|Division of Biological Sciences, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Schulz
mesh_terms: D000109:Acetylcholine; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007328:Insulin; D020738:Leptin / Q000097:blood* / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012737:Sex Factors; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology*; D014655:Vascular Resistance
chemical_list: D007328:Insulin; D020738:Leptin; D000109:Acetylcholine