Location: Arkansas Children's Nutrition CenterTitle: Maternal overweight induces integrative changes in gene expression in the offspring in metabolically active tissues Author
Submitted to: Annual Scientific Meeting NAASO, The Obesity Society
Publication Type: Abstract Only
Publication Acceptance Date: 6/7/2010
Publication Date: 11/11/2010
Citation: Shankar, K., Kang, P., Harrell, A., Zhong, Y., Ronis, M.J., Badger, T.M. 2010. Maternal overweight induces integrative changes in gene expression in the offspring in metabolically active tissues. Obesity. 18(S2):S74. Interpretive Summary:
Technical Abstract: Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult-life. Male offspring from OW rat dams (Sprague Dawley) gain greater body weight (p less than 0.005), fat mass and develop insulin resistance when fed high-fat diets (45 percent fat). Hepatic microarray analyses at postnatal day 21, revealed a reprogramming of lipogenic and lipid degradative pathways following exposure to maternal OW. This was associated with increased expression of SREBP-1 and 20 downstream lipogenic effectors, and decreased PPAR-alpha/AMPK signaling. Serum levels of FGF21 and high mol wt adiponectin (p less than 0.05), were also decreased in OW dam offspring at weaning. In this report, we examined the global gene expression changes in white adipose tissue (WAT) and gastrocnemius skeletal muscle (SM) of offspring at PND21, using Affymetrix GeneChip Rat 230 2.0 microarrays. Exposure to maternal OW altered the expression of 258 transcripts in the offspring WAT (compared to 147 transcripts in the liver). Strikingly the expression of lipogenic transcripts was commonly upregulated in both WAT and liver, but not in the SM. Gene expression was confirmed using real-time PCR. Expression of FASN (3-fold), SREBP-1(1.7-fold), ChREBP (2.5-fold), ACLY (4.5-fold), ELOVL6 (3.6-fold), adiponutrin (4.8-fold) in the WAT was increased (p less than 0.05), consistent with expression increases in the liver. Expression of the adipogenic factor PPAR-gamma 2 was unchanged in WAT. In contrast, SM gene expression in the offspring of OW dams did not show increased lipogenic genes. However, mRNA expression of UCP-2 was decreased (p less than 0.05) in both liver (3-fold) and SM (1.7-fold) in offspring of OW dams. Further, mRNA levels of UCP-1 (1.7fold) were significantly lower in brown adipose tissue of OW dam offspring. Our findings strongly suggest that maternal obesity coordinately increases lipogenic profiles in the liver and WAT, and programs multiple aspects of energy-balance regulation in the offspring.