title: Evidence for transgenerational metabolic programming in Drosophila.
abstract: Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie) feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon.
authors: Department of Pediatrics, and.
authors: Jessica L
authors: JL
authors: Buescher
authors: Laura P
authors: LP
authors: Musselman
authors: Christina A
authors: CA
authors: Wilson
authors: Tieming
authors: T
authors: Lang
authors: Madeline
authors: M
authors: Keleher
authors: Thomas J
authors: TJ
authors: Baranski
authors: Jennifer G
authors: JG
authors: Duncan
mesh_terms: D000818:Animals; D001823:Body Composition; D002241:Carbohydrates / Q000097:blood; D003433:Crosses, Genetic; D004032:Diet; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D004843:Epistasis, Genetic / Q000235:genetics; D005247:Feeding Behavior; D005260:Female; D020869:Gene Expression Profiling; D040941:Heredity / Q000235:genetics*; D040582:Inheritance Patterns / Q000235:genetics*; D007814:Larva; D008297:Male; D008660:Metabolism / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000473:pathology; D010641:Phenotype
chemical_list: D002241:Carbohydrates
references: Mol Cell Biol. 2010 Feb;30(3):793-805
references: 19933845
references: Mol Cell. 2004 Nov 19;16(4):641-53
references: 15546623
references: J Biol. 2003;2(3):20
references: 12908874
references: Gene. 2009 Oct 1;446(1):11-7
references: 19573582
references: Biol Reprod. 2009 Apr;80(4):622-30
references: 19129514
references: Diabetes. 2001 Oct;50(10):2279-86
references: 11574409
references: J Mol Cell Cardiol. 2013 Feb;55:117-29
references: 23266593
references: Genes Dev. 2009 Dec 1;23(23):2711-6
references: 19952106
references: Prog Mol Biol Transl Sci. 2011;101:177-91
references: 21507351
references: J Matern Fetal Neonatal Med. 2010 Mar;23(3):199-203
references: 20121460
references: Cell Metab. 2009 Dec;10(6):481-90
references: 19945405
references: Physiol Rev. 2005 Apr;85(2):571-633
references: 15788706
references: Circulation. 2012 Mar 20;125(11):1381-9
references: 22344037
references: Cell Metab. 2010 Nov 3;12(5):533-44
references: 21035763
references: Nutr Res. 2010 Jun;30(6):418-26
references: 20650350
references: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12691-6
references: 17652514
references: Diabetes Care. 2010 Aug;33(8):1845-9
references: 20435793
references: Dis Model Mech. 2011 Nov;4(6):842-9
references: 21719444
references: PLoS Genet. 2013;9(1):e1003175
references: 23326243
references: Obes Res. 2005 Jan;13(1):163-9
references: 15761176
references: Methods Cell Biol. 1994;44:565-73
references: 7535884
references: J Exp Biol. 2007 Mar;210(Pt 6):956-63
references: 17337708
references: PLoS Genet. 2007 Nov;3(11):e199
references: 18081423
references: Insect Biochem Mol Biol. 2009 Aug;39(8):547-67
references: 19540341
references: Obesity (Silver Spring). 2009 May;17(5):1032-9
references: 19148128
references: J Mol Biol. 1998 Mar 13;276(5):877-85
references: 9566193
references: Biochem Soc Trans. 2008 Oct;36(Pt 5):935-40
references: 18793164
references: Nat Rev Endocrinol. 2009 Nov;5(11):604-10
references: 19786987
references: Endocrinology. 2011 Apr;152(4):1378-87
references: 21303952
references: Int J Obes (Lond). 2008 Sep;32(9):1373-9
references: 18626486
references: Circulation. 2010 Jun 15;121(23):2557-64
references: 20516377
references: Biochem J. 2010 Apr 14;427(3):333-47
references: 20388123
references: Curr Diab Rep. 2012 Feb;12(1):67-74
references: 22127642
references: N Engl J Med. 2011 Nov 17;365(20):1876-85
references: 22087679
references: Cell Metab. 2007 Oct;6(4):257-66
references: 17908555
references: PLoS One. 2012;7(5):e36583
references: 22567167
references: Mol Endocrinol. 2011 Jan;25(1):83-91
references: 21084378
references: J Neuroendocrinol. 2010 Aug;22(8):905-14
references: 20403085
references: Neuroendocrinology. 2011;93(1):1-8
references: 21079387
references: Cell Metab. 2009 Mar;9(3):228-39
references: 19254568
references: N Engl J Med. 2007 Dec 6;357(23):2329-37
references: 18057335
references: Diabetes. 2009 May;58(5):1116-25
references: 19188431
references: PLoS Genet. 2012 Jan;8(1):e1002478
references: 22275878
references: J Hepatol. 2012 Apr;56(4):900-7
references: 22173165