Glucose metabolism is altered in the adequately-nourished grand-offspring (F3 generation) of rats malnourished during gestation and perinatal life
To the Editor:
A growing number of experimental animal studies have demonstrated the intergenerational effects of foetal/perinatal programming on birth weight, blood pressure and glucose metabolism. Potential explanations for these intergenerational effects include the following: (1) shared genetic attributes of parent and offspring; (2) adverse ‘extrinsic’ environmental conditions that persist across generations; and (3) adverse intrauterine environments that may be propagated across generations .
While a large number of animal studies have shown the effects of undernutrition during foetal/perinatal development on the glucose metabolism of exposed animals (F1) in adulthood , several studies have shown that glucose metabolism is also altered in the offspring (F2) of foetally malnourished F1 females, even when the F1 females have been well nourished since weaning [3, 4]. Here, we show, for the first time, that the glucose metabolism of the grand-offspring (F3) of female rats malnourished during development is also adversely affected.
Sprague–Dawley rats consumed either a nutritionally adequate diet (20% protein; TD 91352; Harlan Teklad, Madison, WI, USA), or an isoenergetic, low-protein diet (8% protein; TD 93033; Harlan Teklad) from day 1 of pregnancy through lactation. Pups that were protein malnourished in utero consumed an adequate unrestricted diet post-weaning. The dams of control pups were adequately nourished throughout pregnancy and their offspring consumed an adequate unrestricted diet post-weaning. To conserve animal resources, only one generation of control animals was bred. At ∼70 days of age, control and experimental animals were deprived of food overnight and subjected to an i.p. glucose tolerance test. Animals were killed under CO2 anaesthesia at 0, 30 and 120 min after glucose load (30% w/v; 2 g/kg body weight, i.p.). Blood was collected by cardiac puncture. Four female first-generation (F1) rats, whose mothers were protein-malnourished both during pregnancy and while nursing, were randomly selected from the experimental group at ∼70 days of age. The selected F1 rats were mated with control breeder males and maintained on the adequate diet throughout gestation and lactation. Their offspring, the F2 generation, also consumed an adequate diet post-weaning. At ∼70 days of age, glucose tolerance tests were conducted on the F2 rats as described above. A final generation of animals (F3) was bred from control breeder males and four randomly selected F2 dams whose mothers (F1) had been protein-malnourished throughout pregnancy and lactation. F3 animals were maintained on the adequate diet and tested as described. This research was approved by the Institutional Animal Care and Use Committee (IACUC) at Arizona State University. Animals were maintained in accordance with the ‘Guide for the Care and Use of Laboratory Animals’ of the National Research Council (7th ed., 1996).
Plasma glucose and insulin concentrations in control rats and in rats whose dams consumed low-protein diets during gestation (F1), offspring of F1 rats (F2), and offspring of F2 rats (F3)
Plasma glucose (mmol)
Plasma insulin (mIU)
This research was funded by a Research Incentive Award of the Vice Provost for Research at Arizona State University.
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