Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity
- Meena Garg1,
- Manikkavasagar Thamotharan1,
- Yun Dai1,
- Shanthie Thamotharan1,
- Bo Chul Shin1,
- David Stout2 and
- Sherin U. Devaskar1⇓
- 1Division of Neonatology and Developmental Biology, Neonatal Research Center, David Geffen School of Medicine at University of California, Los Angeles, California
- 2Department of Pediatrics and Crump Institute for Molecular Imaging, David Geffen School of Medicine at University of California, Los Angeles, California
- Corresponding author: Sherin U. Devaskar, .
Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation–induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal (PN)1 to PN21) postnatal caloric limitation with growth restriction (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, and inactive and exhibiting metabolic inflexibility (Vo2) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype.