title: Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates.
abstract: Maternal obesity is thought to increase the offspring's risk of juvenile obesity and metabolic diseases; however, the mechanism(s) whereby excess maternal nutrition affects fetal development remain poorly understood. Here, we investigated in nonhuman primates the effect of chronic high-fat diet (HFD) on the development of fetal metabolic systems. We found that fetal offspring from both lean and obese mothers chronically consuming a HFD had a 3-fold increase in liver triglycerides (TGs). In addition, fetal offspring from HFD-fed mothers (O-HFD) showed increased evidence of hepatic oxidative stress early in the third trimester, consistent with the development of nonalcoholic fatty liver disease (NAFLD). O-HFD animals also exhibited elevated hepatic expression of gluconeogenic enzymes and transcription factors. Furthermore, fetal glycerol levels were 2-fold higher in O-HFD animals than in control fetal offspring and correlated with maternal levels. The increased fetal hepatic TG levels persisted at P180, concurrent with a 2-fold increase in percent body fat. Importantly, reversing the maternal HFD to a low-fat diet during a subsequent pregnancy improved fetal hepatic TG levels and partially normalized gluconeogenic enzyme expression, without changing maternal body weight. These results suggest that a developing fetus is highly vulnerable to excess lipids, independent of maternal diabetes and/or obesity, and that exposure to this may increase the risk of pediatric NAFLD.
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: McCurdy
authors.forename: Jacalyn M
authors.initials: JM
authors.lastname: Bishop
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Williams
authors.forename: Bernadette E
authors.initials: BE
authors.lastname: Grayson
authors.forename: M Susan
authors.initials: MS
authors.lastname: Smith
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Friedman
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004041:Dietary Fats / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism*; D005943:Gluconeogenesis; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008251:Macaca; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000150:complications; D018384:Oxidative Stress; D011247:Pregnancy; D014280:Triglycerides / Q000378:metabolism
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D020738:Leptin; D014280:Triglycerides