There is emerging evidence supporting fetal metabolism is determined in utero, and the programmed metabolism persists into adulthood. Understanding how metabolic dysfunction is transmitted through generations will help identify the biological mechanisms underlying obesity and cardiometabolic disease, and provide insight regarding rational strategies for treatment and prevention.

Metabolic parameters were assessed in offspring from dams fed different diets for 4 weeks before pregnancy and during pregnancy and lactation; open standard (OSD), isocaloric low protein (LPD, 8% protein) and high-fat diets (HFD, 60% fat). After weaning, offspring had OSD.

Offspring from dams fed LPD showed 31% reduced birthweights compared to offspring from dams fed OSD, and the difference persisted into 6 months of age. At 3 and 6 months, they exhibited significantly smaller perigonadal fat pad than offspring from dams fed OSD. In addition, they showed significantly higher blood glucose concentration than offspring from dams fed OSD at birth (52.35mg/dl vs. 63.71 mg/dl). In case of offspring from dams fed HFD, they exhibited significantly higher body weights (5.99g vs. 6.56g) and blood glucose level at birth (52.35mg/dl vs. 64.64 mg/dl) compared to offspring from dams fed OSD. The difference of body weights continued to 3week-old at weaning, and they showed significantly impaired glucose tolerance compared to offspring from dams fed OSD at the same age.

Maternal dietary manipulation strongly influenced metabolic phenotypes such as birthweight, blood glucose concentration at birth and glucose tolerance, and the programed phenotypes persisted into adulthood. Therefore, maternal nutrition programs a glucose intolerant phenotype in offspring indicating that in utero stress augments diabetes risk not only childhood but also adulthood. We expect our findings in this study to help clarify the mechanism how the utero environment affects offspring’s metabolism, which would explain in part the intergenerational transmission of obesity.


M. Kang: None. J.P. Antipenko: None. X. Liu: None. K.M. Habegger: Consultant; Self; Glyscend, Inc.. Research Support; Self; Glyscend, Inc.. Consultant; Self; Intarcia Therapeutics, Inc. W. Garvey: Advisory Panel; Self; Novo Nordisk Inc., Merck & Co., Inc.. Research Support; Self; Sanofi, Pfizer Inc., Novo Nordisk Inc., AstraZeneca, Merck & Co., Inc., Elcelyx Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Eisai Inc..

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