title: Maternal Hyperleptinemia Improves Offspring Insulin Sensitivity in Mice.
abstract: Maternal obesity and gestational diabetes are prevalent worldwide. Offspring of mothers with these conditions weigh more and are predisposed to metabolic syndrome. A hallmark of both conditions is maternal hyperleptinemia, but the role of elevated leptin levels during pregnancy on developmental programming is largely unknown. We previously found that offspring of hyperleptinemic mothers weighed less and had increased activity. The goal of this study was to determine whether maternal leptin affects offspring insulin sensitivity by investigating offspring glucose metabolism and lipid accumulation. Offspring from two maternal hyperleptinemic models were compared. The first model of hyperleptinemia is the Lepr(db/+) mouse, which has a mutation in one copy of the gene that encodes the leptin receptor, resulting in a truncated long form of the receptor, and hyperleptinemia. Wild-type females served as the control for the Lepr(db/+) females. For the second hyperleptinemic model, wild-type females were implanted with miniosmotic pumps, which released leptin (350 ng/h) or saline (as the control) just prior to mating and throughout gestation. In the offspring of these dams, we measured glucose tolerance; serum leptin, insulin, and triglyceride levels; liver triglycerides; pancreatic α- and β-cell numbers; body composition; incidence of nonalcoholic fatty liver disease; and the expression of key metabolic genes in the liver and adipose tissue. We found that the offspring of hyperleptinemic dams exhibited improved glucose tolerance, reduced insulin and leptin concentrations, reduced liver triglycerides, and a lower incidence of nonalcoholic fatty liver disease. Overall, maternal hyperleptinemia was beneficial for offspring glucose and lipid metabolism.
authors.affiliation: Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201.
authors.forename: Omonseigho O
authors.initials: OO
authors.lastname: Talton
authors.affiliation: Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Pennington
authors.affiliation: Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Pollock
authors.affiliation: Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201.
authors.forename: Keenan
authors.initials: K
authors.lastname: Bates
authors.affiliation: Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201.
authors.forename: Lixin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Ellersieck
authors.affiliation: Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Schulz
mesh_terms: D000818:Animals; D005260:Female; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D051379:Mice; D009154:Mutation; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D007328:Insulin; D020738:Leptin; D054411:Receptors, Leptin; D014280:Triglycerides