Perinatal maternal hypercaloric diets increase the susceptibility to metabolic disorders in the offspring. We hypothesized that maternal intake of an isocaloric moderate-fat diet (mMFD) would disturb the
glucose homeostasis and favor the β-cell failure in response to
fructose overload in adult male offspring.
METHODS: Female Wistar rats received an isocaloric diet (3.9 kcal/g) containing 29 % (mMFD) or 9 % as fat (mSTD) prior mating and throughout gestation and lactation. After weaning, male offspring received standard chow and
fructose-
drinking water (15 %) between 120 and 150 days old.
KEY FINDINGS: mMFD offspring had higher
body weight, visceral adiposity and, fasting glycemia, with normal insulinemia.
Fructose increased glycemia at 15 min from oral
glucose administration, but only mMFD had returned to basal
glucose levels at 120 min.
Fructose increased HOMA-IR index regardless diet, but only mMFD exhibited
hyperinsulinemia and a higher HOMA-β index. mMFD pancreatic islets showed increased area and
insulin immunostaining density, suggesting β-cell
hypertrophy.
Fructose induced the expected compensatory
hypertrophy in mSTD islets, while the opposite occurred in mMFD islets, associated with reduced
insulin immunostaining, suggesting lower
insulin storage. Pancreatic islets isolated from mMFD offspring exhibited higher
glucose-stimulated
insulin release at physiological concentrations. However, at higher
glucose concentrations, the islets from
fructose-treated mMFD reduced dramatically their
insulin release, suggesting exhaustion.
SIGNIFICANCE: Isocaloric mMFD induced adaptive mechanism in the offspring allowing
insulin hypersecretion, but under metabolic challenge with
fructose, β-cell compensation shifts to exhaustion, favoring dysfunction. Therefore, a maternal MFD may contribute to developing diabetes under
fructose overload in the adult offspring.