Intrauterine exposure to high saturated fat diet elevates risk of adult-onset chronic diseases in C57BL/6 mice.
BACKGROUND
The developmental environment is thought to determine, in part, lifelong metabolic parameters and risk of adult disease. Effects of maternal malnutrition on fetal growth have been studied extensively, and the role of poor prenatal diet in elevating lifelong risk of cardiovascular and metabolic disease has been well characterized (www.thebarkertheory.com). However, the contribution of gestational high saturated fat diet (HFD) to adult-onset metabolic disease and skeletal dysfunction has only recently been recognized, and as such is incompletely understood.


METHODS
The present study evaluates the pathophysiologic mechanisms linking gestational HFD (approximating the macronutrient content of fast food) and elevated oxidative stress (OS) to adult-onset skeletal, cardiovascular, and metabolic dysfunction.


RESULTS
Results of this study demonstrate that adult offspring of dams fed HFD during pregnancy exhibited adult hyperglycemia, insulin resistance, obesity, and hypertension, despite being fed healthy standard rodent chow throughout postnatal life. These offspring also showed significantly lower femoral epiphyseal average bone mineral density (ABMD) at 6 months of age, and dysregulation of distal femoral trabecular architecture at 12 months of age, characteristic of osteoporosis. Incidence of these adult-onset adverse skeletal and metabolic effects was reduced by supplementing the pregnant dam with the antioxidant (quercetin, Q) during pregnancy.


CONCLUSIONS
Collectively, these data suggest that offspring of dams who consume a diet rich in saturated fats during pregnancy are at increased risk of adult-onset chronic disease. Additionally, these chronic diseases were determined to be in-part OS-mediated, and preventable by increasing a prenatal dietary antioxidant; this knowledge offers both a putative mechanism of disease pathogenesis and suggests a potential preventive strategy.
Liang
Chengya
C
VA-MD Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.
Oest
Megan E
ME
Prater
M Renee
MR
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects; D002908:Chronic Disease; D004036:Diet, Atherogenic; D005227:Fatty Acids / Q000008:administration & dosage*; D005260:Female; D007328:Insulin / Q000097:blood; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D011794:Quercetin / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed
D000975:Antioxidants; D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D011794:Quercetin