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Cardiometabolic Risk Factors in the Mouse are Shaped by Metabolic State of the Mother During Pregnancy
Author(s) -
Thompson Jennifer Anne,
Mintz James
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1213.4
Subject(s) - offspring , endocrinology , medicine , weaning , triglyceride , pregnancy , gestational diabetes , leptin , gestation , insulin , cholesterol , obesity , biology , genetics
Objective To determine if gestational diabetes (GDM) programs an aberrant cardiometabolic phenotype in the offspring. Methods At 14 weeks of age and after assessment of pre‐conception metabolic status, female wild type (Wt) and female mice heterozygous for the leptin receptor mutation (Het db ) were mated with Wt males. To confirm development of GDM, intra‐peritoneal glucose tolerance tests (IPGTT) were performed on Gd17 (term = Gd19) in Wt and Het db pregnant females. Maternal body composition was determined by NMR spectroscopy. One group of pregnant females was sacrificed on Gd18 for collection of maternal blood; the second group delivered spontaneously. Only Wt offspring were examined. At 3‐weeks (weaning), 3‐months and 6‐months of age, offspring were evaluated for body composition using NMR. At 6‐months, fasting plasma levels of lipids were determined by Colorimetric assay. Results Prior to conception, regulation of blood glucose appears normal in Het db females compared to Wt controls, yet non‐pregnant Het db females displayed increased adiposity and reductions in lean body mass relative to age‐matched, non‐pregnant controls (p < 0.001). On Gd17 there was an increase in fasting blood glucose, insulin and triglyceride levels, and reduction in glucose clearance in pregnant Het db vs. Wt females (all p < 0.05). At 3‐weeks of age, % body fat was increased in male (p < 0.001) and female (p < 0.001) Wt offspring born from a Het db dam (Male: Wt dam 6.6 ± 0.4 %, Het db dam 10.8 ± 0.8 %; Female: Wt dam 7.0 ± 0.37 %, Het db dam 10.4 ± 0.7 %). At 3‐months and 6‐months, adiposity remained higher in offspring born to Het db dams (p < 0.05). At 6‐months, fasting plasma triglyceride levels were increased 2‐fold in Wt offspring of Het db vs. Wt pregnancies; non‐esterified fatty acids (p < 0.01) and cholesterol (p < 0.05) levels were increased by 54% and 68%, respectively, in Wt offspring of Het db pregnancy. Conclusions The Het db female has high pre‐pregnancy adiposity and spontaneously develops glucose intolerance during pregnancy and thus is a valuable model for the study of GDM. Similar to human GDM, the Het db model programs an abnormal metabolic phenotype in the offspring. Support or Funding Information JAT supported by AHA 15POST25730006JAT