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Objective: Intrauterine growth restriction is associated with increased prevalence of the metabolic syndrome in adult life, including increased adiposity. The aim of this study was to investigate if maternal protein energy malnutrition is associated with changes in expression of genes involved in fat partitioning in weanling rats., Research Methods and Procedures: Time-mated mothers were placed on one of two isocaloric diets, low protein [(LP), 8% protein] or control (20% protein). All mothers remained on the diet throughout pregnancy and lactation. A third group received control for 2 weeks and was switched to LP for the last week of pregnancy and lactation [late low protein (LLP) group]. Offspring were analyzed at weaning for serum glucose, nonesterified fatty acids, triglyceride, and insulin. Expression of the genes acetyl-coenzyme A carboxylase, fatty acid synthase, and carnitine palmitoyl transferase 1 were measured in liver, quadriceps muscle, and subcutaneous white adipose tissue using semiquantitative reverse transcription-polymerase chain reaction., Results: LLP and LP offspring were shorter, weighed less, had reduced serum insulin and nonesterified fatty acids, and had increased serum glucose, serum triglycerides, and hepatic triglycerides. Hepatic gene expression of acetyl-coenzyme A carboxylase and fatty acid synthase was increased 2-fold in LLP and LP offspring (p < 0.001). These changes were not seen in muscle or subcutaneous white adipose tissue. CPT-1 gene expression was unaltered in all tissues examined., Discussion: Maternal protein energy malnutrition programs gene expression of lipogenic enzymes in the liver of weanling offspring in a manner favoring fat synthesis that may predispose these offspring to fat accumulation and insulin resistance later in life.

Objective: Obesity is a major risk factor for the development of type 2 diabetes. Tumor necrosis factor (TNF)-alpha is a candidate gene for the development of both obesity and insulin resistance. We investigated whether a common polymorphism in the promoter region (-308 G/A) of the TNF-alpha gene was associated with increased risk for the development of insulin resistance and cardiovascular disease in an obese Australian population., Research Methods and Procedures: Obese, non-diabetic subjects (146 women and 34 men) were genotyped with polymerase chain reaction-restriction fragment length polymorphism techniques, and anthropometric and biochemical measurements were analyzed. A homeostasis model assessment (HOMA) score was used to gauge the level of insulin resistance., Results: The frequencies of the G allele and the A allele were 0.759 and 0.241, respectively. Subjects homozygous for the A allele had higher fasting insulin levels (226 vs. 131 pM; p < 0.001), higher HOMA scores (10.2 vs. 5.3; p < 0.001), higher systolic blood pressure (143 vs. 129 mm Hg; p = 0.02), and lower high-density lipoprotein (HDL) cholesterol (1.13 vs. 1.25 mM; p = 0.04) than did subjects homozygous for the G allele. Whereas an association between insulin resistance and body mass index or waist circumference was seen in all subjects, a highly significant negative correlation of HDL cholesterol to HOMA scores (r = -0.710; p < 0.001) occurred in subjects with the A allele only., Discussion: The -308 G/A TNF-alpha gene variant conveys an increased risk for the development of insulin resistance in obese subjects. The presence of low HDL cholesterol levels further increases the risks associated with insulin resistance in carriers of the A allele.