NUTRITIONAL REGULATION OF CELL AND ORGAN GROWTH, DIFFERENTIATION, AND DEVELOPMENT
Location: Children Nutrition Research Center (Houston, Tx)
Title: C57BL/6J male offspring exposed "in utero" and during weaning to a maternal low protein diet have reduced muscle weight by 12 months of age
Submitted to: Society for Gynecologic Investigation
Publication Type: Abstract Only
Publication Acceptance Date: February 27, 2007
Publication Date: March 14, 2007
Citation: Fiorotto, M.L., Rosetta, R., Yu, Z., Oliver, W., Van den Veyver, I. 2007. C57BL/6J Male offspring exposed "in utero" and during weaning to a maternal low protein diet have reduced muscle weight by 12 months of age [abstract]. Reproductive Sciences. 14(1)[Suppl]:95A.
Objective: C57BL/6J mice are predisposed to obesity and type 2 diabetes (T2DM) and may be a sensitive model for fetal programming of T2DM. The "maternal low protein diet" (MLP) rat model is well established to study fetal growth restriction effects on programming of T2DM. How data from C57BL/6J mice compare to rat is incompletely known. Here, we evaluate glucose tolerance and tissue weights in C57BL/6J male offspring exposed "in utero" and during suckling to MLP.
Methods: Female mice were fed diets containing 8% (MLP) or 20% protein (control) starting 4 weeks prior to mating. Litters were culled to 6 on day 3 (P3). After weaning, male offspring were single-housed, fed a standard diet and weighed weekly until 12 weeks, then monthly until 1 year. Intraperitoneal glucose tolerance tests were performed at P21, 6 months, and 1 year (n=6 per diet). Mice were sacrificed at 1 year. Heart, kidneys, pancreas, and liver were removed and weighed. Individual hindleg muscles were dissected and weighed. Tibial bone lengths were measured. (Statistics: t-test and ANOVA).
Results: At P365, MLP offspring were lighter than controls (27.7+/-2.5g vs. 31.2+/-1.5g, p=0.02). Weight of organs (as % of total body weight) was not significantly different between MLP and control offspring (heart: 0.69+/-0.13% vs. 0.67+/-0.16%, p=0.77; liver: 4.87+/-0.62% vs. 4.52+/-0.66%, p=0.39; pancreas: 1.01+/-0.13% vs. 0.89+/-0.09%, p=0.12; kidneys: 1.80+/- 0.20% vs. 1.73+/-0.16%, 0.58). Tibiae (18.00+/-0.19mm vs. 18.37+/-0.15mm, p=0.02) were shorter in MLP offspring. Standardized muscle weights (average weight/mm tibia length) were lower for tibialis anterior (2.22+/-0.19g vs. 2.63+/-0.10g, p=0.001), gastrocnemius (6.25+/-0.67g vs. 7.18+/-0.41g, p=0.01), soleus (0.41+/-0.03g vs. 0.49+/-0.03g, p=0.005) and extensor digitorum longus (0.52+/-1.00 vs. 0.62+/-0.04, p=0.05), but not for quadriceps (9.67+/-0.47g vs. 10.67+/-0.57g, p=0.07) and plantaris (1.02+/-0.8g vs. 0.97+/-0.07g, p=0.34) (MLP: n=5; control: n=6). All had abnormal GTT at 6 months and 1 year; there was no difference between MLP and controls.
Conclusions: C57BL/6J males exposed to MLP have lower total body weight and muscle weight at 1 year of age. The molecular change(s) underlying the reduced muscle mass will be studied for their role in programming of T2DM.