Review Article

Intergenerational Cycle of Obesity and Diabetes: How Can We Reduce the Burdens of These Conditions on the Health of Future Generations?

Table 3

Most important interventions performed in pregnant animals to reduce or improve maternal, neonatal, and offspring outcomes.

StudyAnimal modelInterventionMaternal outcomesGestational or obstetrical outcomesNeonatal outcomesLong-term offspring outcome

Dolinoy et al., 2006 Environ Health Perspect [119]Heterozygous viable yellow agouti (Avy) mice
, unsupplemented litters (52 offspring)
, genistein supplemented (44 offspring)
Females (8–10 weeks of age) received phytoestrogen-free modified AIN-93G diet or modified AIN-93G diet supplemented with 250 mg/kg of genistein (comparable to human high-soy diet) Diet provided 2 weeks before mating, throughout pregnancy and lactationN/AN/ADay 21:similar litter size, wean weight, percent survival, sex ratio; maternal supplementation favored pseudoagouti versus full agouti (yellow coat) phenotype ( ) +
↑ Agouti gene methylation
Agouti gene methylation highly correlated between day 21 and 150 in offspring whose mothers received supplement
At week 60: weight in pseudoagouti versus full agouti mice ( )
Pseudoagouti: normal weight versus full agouti (more obese)

Sen et al., 2010 Diabetes [120]Female Sprague-Dawley rats
Diets: control (C, ); control + antioxidant (CAox, ); Western (W, ), high protein + fat (HP + F, ); W + Aox (WAox, )
Female rats received diets from age 4 to 13–15 weeks (end of gestation). Litters culled to 8 pups.
Studies performed in male offspring only. At weaning, offered control diet.
End of gestation:↑ gestational weight gain in dams offered W and WAox versus C; similar glucose and food consumption;↑ insulin, free-fatty acid (FFA) and leptin in W versus C, but in WAox versus WN/AEmbryos:in W versus C: ↑oxidative stress,
in WAox
Birth: similar weight
In W versus C: ↑ FFA, insulin and leptin
2 weeks: in W versus C: ↑ fat mass, FFA, insulin, leptin, proadipogenic, and lipogenic genes expression, but in WAox versus W
2 months: in W versus C:↑ total and central fat mass, insulin, leptin, proadipogenic and lipogenic genes expression, but in WAox versus W; ↑ impaired glucose tolerance, but normalized in WAox (similar to C)

Zambrano, et al. 2010 J Physiol [121]Female albino Wistar rats
; control
; obesogenic;
dietary intervention (DINT)
At 3 weeks, females rats received obesogenic (0; ) or control (C; ) diets
At 90 days, O dams were either continued on O diet ( ) or receiving the C diet (DINT; )
One month after, animals were bred and continued prepregnancy diet throughout pregnancy and lactation
Litters culled to 10 pups; pup sex ratio 1 : 1
N/A90 days:in O and DINT versus C: ↑weight
Breeding and
delivery: in O versus C: ↑weight, but in DINT versus O
Weaning: in O versus C: ↑leptin, but in DINT versus O
Birth and weaning: similar morphometric variable
Weaning: in O versus C: ↑subcutaneous fat tissue, serum triglycerides, leptin, insulin, but in DINT versus O; similar glucose despite ↑ insulin (suggesting insulin resistance), but in DINT versus O
Postnatal day 120: in O versus C: ↑serum glucose, insulin, insulin resistance, but similar glucose with ↑ insulin in DINT versus C (suggesting partial recovery of insulin resistance)
Postnatal day 150: similar body weight
In O versus C: ↑ fat and leptin, larger fat cell size
In DINT versus C: non-significant in fat mass and fat cell size