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Maternal Hyperleptinemia Improves Offspring Insulin Sensitivity in Mice.
- Source :
-
Endocrinology [Endocrinology] 2016 Jul; Vol. 157 (7), pp. 2636-48. Date of Electronic Publication: 2016 May 04. - Publication Year :
- 2016
-
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.
- Subjects :
- Animals
Female
Insulin metabolism
Leptin pharmacology
Liver metabolism
Mice
Mutation
Pancreas metabolism
Pregnancy
Receptors, Leptin genetics
Triglycerides metabolism
Insulin Resistance physiology
Leptin blood
Non-alcoholic Fatty Liver Disease metabolism
Prenatal Exposure Delayed Effects metabolism
Receptors, Leptin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 157
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 27145007
- Full Text :
- https://doi.org/10.1210/en.2016-1039