Effects of postweaning calorie restriction on accelerated growth and adiponectin in nutritionally programmed microswine offspring

Abstract

Poor prenatal development, followed by rapid childhood growth, conveys greater cardiometabolic risk in later life. Microswine offspring exposed to perinatal maternal protein restriction [MPR; "low protein offspring" (LPO)] grow poorly in late-fetal/neonatal stages. After weaning to an ad libitum (AL) diet, LPO-AL exhibit accelerated growth and fat deposition rates with low adiponectin mRNA, despite low-normal body fat and small intra-abdominal adipocytes. We examined effects of caloric restriction (CR) on growth and metabolic status in LPO and normal protein offspring (NPO) randomized to AL or CR diets from weaning. CR transiently reduced growth in both LPO and NPO, delaying recovery in female LPO-CR. Over 7.5-12.5 weeks, linear growth rates in LPO-CR were slower than LPO-AL ( P < 0.001) but exceeded NPO-AL; body weight growth rates fell but were lower in LPO-CR versus NPO-CR. Linear acceleration ceased after 12 weeks. At 16 weeks, percent catch-up in LPO-CR was reduced versus LPO-AL ( P < 0.001). Plasma growth hormone was low in LPO ( P < 0.02). CR normalized fat deposition rate, yet adiponectin mRNA remained low in LPO-CR ( P < 0.001); plasma adiponectin was low in all LPO-AL and in female LPO-CR. Insulin sensitivity improved during CR. We conclude that in LPO: 1) CR delays onset of, but does not abolish, accelerated linear growth, despite low growth hormone; 2) CR yields stunting via delayed onset, plus a finite window for linear growth acceleration; 3) MPR lowers adiponectin mRNA independently of growth, adiposity, or adipocyte size; and 4) MPR reduces circulating adiponectin in LPO-AL and female LPO-CR, potentially enhancing cardiometabolic risk.

Altered vertebral and femoral bone structure in juvenile offspring of microswine subject to maternal low protein nutritional challenge

“…Nevertheless, body length was reduced by a consistent amount by calorie restriction (DuPriest et al. ), suggesting bone size, but not structure, was altered by calorie restriction.…”

“…(DuPriest et al. 2012b, ). The suggestion of accelerated bone development (see above) is in conjunction with accelerated whole‐body growth in crown‐rump length from 5 to 12 weeks of age.…”

“…However, as low protein offspring also exhibited increased feed utilization efficiency, the amount of feed offered was adjusted as necessary every 2–3 days, never falling below 20 g/kg, to maintain calorie restricted offspring on the projected growth trajectory (DuPriest et al. ). Thus the degree of caloric restriction averaged 20–25% of control dietary intake.…”

“…Average feed intake (g/kg) across the period of caloric restriction did not differ between low protein and normal protein offspring (DuPriest et al. ).…”

“…At 6 weeks (when weights were most reduced in low protein offspring vs. control offspring in pilot studies) and 11 weeks (when weights were statistically similar between low protein offspring and control offspring in pilot studies), bone mineral content and bone mineral density were assessed by dual‐energy x‐ray absorptiometry (DEXA) (DuPriest et al. 2012b, ). Piglets were anesthetized by inhaled isoflurane (2.0–2.5% isoflurane, up to 3.0% during the first minutes of induction, with an oxygen flow rate of 2.0 L/min) and placed prone on the DEXA scanner (Hologic QDR‐4500W).…”