Maternal Under-Nutrition During Pregnancy Alters the Molecular Response to Over-Nutrition in Multiple Organs and Tissues in Juvenile Offspring

Previous studies suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We examined whether NHP juvenile offspring of pregnancies with maternal undernutrition (MUN) had altered response to a high-fat, high-carbohydrate diet plus sugar drink challenge (HFCS) compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation, and weaned offspring fed chow diet ad libitum. Offspring of MUN were growth restricted at birth. At [~]4.5y offspring received a 7-week HFCS challenge. Baseline and HFCS gene expression in liver, omental fat, and skeletal muscle, liver glycogen content, and fat cell size were quantified. MUN offspring had lower BMI and liver glycogen compared with CON. Pathway analysis showed differences for skeletal muscle and liver, including hepatic splicing and unfolded protein response. MUN offspring consumed more sugar drink than CON. After HFCS, MUN BMIs were similar to CON. Liver showed coordinated response to HFCS in CON but not MUN. Pathway and liver glycogen differences between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin concentrations, omental adipocyte cell size, liver glycogen content, and tissue-specific molecular response to HFCS challenge suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet. O_FIG O_LINKSMALLFIG WIDTH=172 HEIGHT=200 SRC="FIGDIR/small/548121v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@b15085org.highwire.dtl.DTLVardef@11d4c1dorg.highwire.dtl.DTLVardef@704209org.highwire.dtl.DTLVardef@1ff9791_HPS_FORMAT_FIGEXP M_FIG C_FIG