Maternal obesity can influence susceptibility to
obesity and
type 2 diabetes in progeny. We examined the relationship of maternal
insulin resistance (IR), a metabolically important consequence of increased adiposity, to adverse consequences of
obesity for fetal development. We used mice heterozygous for a null allele of the
insulin receptor (Insr) to study the contributions of maternal IR to offspring phenotype without the potential confound of
obesity per se, and how maternal consumption of high-fat diet (HFD) may, independently and interactively, affect progeny. In progeny fed a 60% HFD,
body weight and adiposity were transiently (5-7 weeks) increased in wild-type (+/+) offspring of Insr(+/-) HFD-fed dams compared to offspring of wild-type HFD-fed dams. Offspring of HFD-fed wild-type dams had increased
body weight,
blood glucose, and plasma
insulin concentrations compared to offspring of chow-fed wild-type dams. Quantification of
proopiomelanocortin (
POMC) and
neuropeptide-Y (NPY) populations in the arcuate nucleus of the hypothalamus (ARH) of offspring of wild-type vs. Insr(+/-) dams was performed to determine whether maternal IR affects the formation of central feeding circuits. We found a 20% increase in the number of
Pomc-expressing cells at postnatal day 9 in offspring of Insr(+/-) dams. In conclusion, maternal HFD consumption-distinct from overt
obesity per se-was a major contributor to increased
body weight, adiposity, IR, and liver
triglyceride (TG) phenotypes in progeny. Maternal IR played a minor role in predisposing progeny to
obesity and IR, though it acted synergistically with maternal HFD to exacerbate early
obesity in progeny.