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Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring

By Junlong Zhang, F. (Fang) Zhang, Xavier Didelot, Kimberley D. Bruce, Felino R. Cagampang, Manu Vatish, Mark A. Hanson, Hendrik Lehnert, Antonio Ceriello and Christopher D. Byrne


Background\ud \ud miRNAs play important roles in the regulation of gene functions. Maternal dietary modifications during pregnancy and gestation have long-term effects on the offspring, but it is not known whether a maternal high fat (HF) diet during pregnancy and lactation alters expression of key miRNAs in the offspring.\ud Results\ud \ud We studied the effects of maternal HF diet on the adult offspring by feeding mice with either a HF or a chow diet prior to conception, during pregnancy and lactation, and all offspring were weaned onto the same chow diet until adulthood. Maternal HF fed offspring had markedly increased hepatic mRNA levels of peroxisome proliferator activated receptor-alpha (ppar-alpha) and carnitine palmitoyl transferase-1a (cpt-1a) as well as insulin like growth factor-2 (Igf2). A HF diet induced up-regulation of ppar-alpha and cpt-1a expression in the wild type but not in Igf2 knock out mice. Furthermore, hepatic expression of let-7c was also reduced in maternal HF fed offspring. Among 579 miRNAs measured with microarray, ~23 miRNA levels were reduced by ~1.5-4.9-fold. Reduced expression of miR-709 (a highly expressed miRNA), miR-122, miR-192, miR-194, miR-26a, let-7a, let7b and let-7c, miR-494 and miR-483* (reduced by ~4.9 fold) was validated by qPCR. We found that methyl-CpG binding protein 2 was the common predicted target for miR-709, miR-let7s, miR-122, miR-194 and miR-26a using our own purpose-built computer program.\ud Conclusion\ud \ud Maternal HF feeding during pregnancy and lactation induced co-ordinated and long-lasting changes in expression of Igf2, fat metabolic genes and several important miRNAs in the offspring

Topics: QH426
Publisher: BioMed Central Ltd.
Year: 2009
OAI identifier:

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  1. (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature doi
  2. (2005). and low-carbohydrate diet during pregnancy and lactation modulates hepatic lipid metabolism in female adult offspring. doi
  3. (1993). Bergström R: Trends in body mass index and prevalence of obesity doi
  4. (2003). Burge CB: Prediction of mammalian microRNA targets. Cell doi
  5. (1998). CL: Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int J Obes Relat Metab Disord doi
  6. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature
  7. (2003). DP: The microRNAs of Caenorhabditis elegans. Genes Dev
  8. Dr Atkins New Diet Revolution. doi
  9. (2006). DZ: The role of microRNA-1 and microRNA133 in skeletal muscle proliferation and differentiation. Nat Genet doi
  10. (2007). Fang F: Over-expression of miR29, highly upregulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Mol Endocrinol doi
  11. H: Global Prevalence of Diabetes: Estimates for the year 2000 and projections for doi
  12. (2006). Lodish HF: Myogenic factors that regulate expression of muscle-specific microRNAs. doi
  13. (2004). MicroRNA-143 Regulates Adipocyte Differentiation. doi
  14. (2006). MicroRNAs: A new class of regulatory genes affecting metabolism. Cell Metab doi
  15. (2007). Obesity and reproduction: impact and interventions. Curr Opin Obstet Gynecol
  16. (2003). PA: siRNAs can function as miRNAs. Genes Dev doi
  17. (2005). Plasterk RHA: MicroRNA function in animal development. doi
  18. (2008). Rajewsky N: Widespread changes in protein synthesis induced by microRNAs. Nature doi
  19. (2005). Ribo-gnome: the big world of small RNAs. Science doi
  20. (1993). Ruvkun G: Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell doi
  21. (2003). S: A randomized trial of a low-carbohydrate diet for obesity. doi
  22. (2005). Silencing of microRNAs in vivo with 'antagomirs'. Nature doi
  23. (2006). Slack FJ: MicroRNA control of lifespan and metabolism. Cell Cycle doi
  24. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell doi
  25. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN14 protein synthesis after the initiation of translation. Dev Biol doi
  26. (1997). Time trends in obesity: an epidemiological perspective. Horm Metab Res doi
  27. (2001). Tuschl T: Identification of novel genes coding for small expressed RNAs. Science doi
  28. (2003). Tuschl T: New microRNAs from mouse and human. RNA doi
  29. (2007). Unraveling the complex regulation of stem cells: implications for aging and cancer. Leukemia doi
  30. (2008). Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. doi
  31. (2006). Wollheim CB: MicroRNAs: 'ribo-regulators' of glucose homeostasis. Nat Med doi
  32. (2007). WY: Impact of tiny miRNAs on cancers.

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