The Role of Insulin-Like Growth Factor II Gene in Diet-Induced Obesity in the Adult Mouse

IGF2 plays an important role in fetal growth.  Inactivation of the paternal IGF2 allele in mice (Igf2^-/- mice) results in growth retardation at birth, whereas IGF2 over-expression results in overgrowth.  Patients with Silver-Russell syndrome, an imprinting disorder that leads to intrauterine growth retardation, are associated with lean bodies and low IGF2 expression.  Several studies have associated insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2/IMP2) with type 2 diabetes and central obesity. We used Igf2^-/- mice to examine the role of IGF2 in obesity.  Two month-old Igf2^-/-  and Igf2^+/+ mice were fed a D1251 Research high fat diet (45% total calories from fat) or standard Prolab diet (23% calories from fat) for 10 weeks.  Our data showed Igf2^-/- mice were smaller in length than Igf2^+/+ littermates (8.2 vs. 9.4 cm, P<0.0001), weighed less (19 vs. 30 gm, respectively, P<0.0001), and ate less than WT mice (2.2 vs. 3.11 gm/day, P<0.001).  When normalized by weight, the Igf2^-/- mice appear to consume more food throughout the study.  The amount of fat both genotypes accumulated after 10 weeks of high fat diet was not significantly different.  DEXA scans showed, however, that Igf2^-/- mice had significant lower bone mineral content (0.414 vs. 0.621 gm, P<0.001) and bone mineral density (0.053 vs. 0.063 gm/cm², P<0.0002) than Igf2^+/+ mice.  Further micro CT scan studies showed that the cranial sutures of Igf2^-/- mice were not completely closed as compared to controls.  Results from these studies support a role of IGF-II bone development but not in diet-induced obesity.