title: The Regulation of Leptin, Leptin Receptor and Pro-opiomelanocortin Expression by N-3 PUFAs in Diet-Induced Obese Mice Is Not Related to the Methylation of Their Promoters.
abstract: BACKGROUND
  The expression of leptin is increased in obesity and inhibited by n-3 polyunsaturated fatty acids (n-3 PUFAs), but the underlying molecular mechanisms have not been firmly established.
  
  
  METHODS
  In this study, we investigated the effects of dietary n-3 PUFAs on the methylation of CpG islands in the promoter regions of the leptin, leptin-R and POMC genes, as well as the effects of n-3 PUFA status in early life on the modification of the promoters of these three genes. Male C57 BL/6J mice were fed a high-fat diet with one of four different fat types: sunflower oil (n-3 PUFA deficient), soy oil, fish oil, or a mixture of soy and fish oil (soy:fish oil = 1:1). Two low-fat diets with sunflower oil or soy oil served as controls. Female mice were fed two breeding diets, sunflower oil or a mixture of soy and fish oil (soy:fish oil = 1:1), during pregnancy and lactation to breed new pups.
  
  
  RESULTS
  Compared to mice fed the control diets, the expression of leptin in fat tissue and leptin-R and POMC in the hypothalamus was higher in the diet-induced obesity (DIO) mice, and the n-3 PUFAs in the diets reversed these elevated expression levels. The mean methylation levels of CpG sites in the promoter regions of the leptin and POMC genes showed no difference between the DIO and the control diet groups nor between the n-3 PUFA-containing and -deficient diet groups. For the CpG sites in the promoter regions of leptin-R, no methylation was found in any of the DIO or control groups. Feeding mice with the n-3 PUFA diet during pregnancy and lactation did not affect CpG methylation in the leptin or POMC promoters.
  
  
  CONCLUSIONS
  Our findings indicate that promoter DNA methylation may not be related to the expression of leptin, leptin-R or its related hypothalamic satiety regulator POMC.
authors: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors: Chaonan
authors: C
authors: Fan
authors: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors: Xinli
authors: X
authors: Liu
authors: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors: Wenwen
authors: W
authors: Shen
authors: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, USA.
authors: Richard J
authors: RJ
authors: Deckelbaum
authors: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors: Kemin
authors: K
authors: Qi
references: Endocrinology. 2006 Jan;147(1):599-606
references: 16210371
references: J Clin Endocrinol Metab. 2002 Nov;87(11):5008-14
references: 12414865
references: Biomed Pharmacother. 2006 Nov;60(9):502-7
references: 17045449
references: J Pediatr Gastroenterol Nutr. 2009 Mar;48 Suppl 1:S31-8
references: 19214056
references: Am J Cardiol. 2006 Aug 21;98(4A):27i-33i
references: 16919514
references: J Biol Chem. 2001 Jun 8;276(23):20197-205
references: 11274167
references: Lipids. 2003 Oct;38(10):1023-9
references: 14669966
references: Am J Clin Nutr. 2007 Sep;86(3):542-8
references: 17823415
references: Obes Rev. 2009 Jul;10(4):383-92
references: 19413700
references: Br J Nutr. 2007 Jun;97(6):1036-46
references: 17381976
references: Semin Vasc Med. 2005 Feb;5(1):15-24
references: 15968576
references: Am J Physiol Endocrinol Metab. 2002 Jun;282(6):E1352-9
references: 12006366
references: J Neuroendocrinol. 2007 May;19(5):364-73
references: 17425611
references: J Biol Chem. 2002 Nov 22;277(47):45420-7
references: 12213831
references: Obes Rev. 2004 Feb;5(1):21-6
references: 14969504
references: J Physiol Biochem. 2009 Mar;65(1):1-9
references: 19588726
references: Prog Lipid Res. 2006 May;45(3):203-36
references: 16516300
references: Biochim Biophys Acta. 2005 May 30;1740(2):266-86
references: 15949694
references: J Endocrinol. 2006 May;189(2):355-63
references: 16648302
references: Organogenesis. 2010 Jan-Mar;6(1):24-32
references: 20592862
references: Metabolism. 2010 Jun;59(6):787-95
references: 20005540
references: Am J Physiol. 1997 May;272(5 Pt 2):R1365-70
references: 9176325
references: Circulation. 2002 Jul 16;106(3):289-91
references: 12119240
references: Kobe J Med Sci. 2009 Mar 10;54(5):E241-9
references: 19628964
references: Diabetes Obes Metab. 2004 Jan;6(1):35-44
references: 14686961
references: Br J Nutr. 2009 Jan;101(2):151-2
references: 18680628
references: Bioinformatics. 2004 Nov 22;20(17):3005-12
references: 15247106
references: Epigenetics. 2006 Oct-Dec;1(4):155-62
references: 17965621
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1682-8
references: 15650121
references: Obes Rev. 2009 Nov;10(6):648-59
references: 19460115
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: J Biol Chem. 2006 Jun 23;281(25):17180-17188
references: 16613853
references: Genes Dev. 2004 Jun 1;18(11):1263-71
references: 15175259
references: J Investig Med. 2009 Oct;57(7):789-94
references: 20029269
references: Am J Clin Nutr. 2006 Jun;83(6 Suppl):1520S-1525S
references: 16841862
references: Obesity (Silver Spring). 2008 Aug;16(8):1763-9
references: 18551122
references: J Nutr. 2002 Aug;132(8 Suppl):2393S-2400S
references: 12163699
references: Cell. 2005 Aug 26;122(4):517-27
references: 16122420
references: Am J Clin Nutr. 2007 May;85(5):1267-74
references: 17490962
references: Reprod Toxicol. 2007 Apr-May;23(3):297-307
references: 17046196
references: J Nutr. 2002 Aug;132(8):2235-40
references: 12163668
references: Essays Biochem. 2001;37:45-57
references: 11758456
references: Horm Res. 2009 Jan;71 Suppl 1:13-6
references: 19153498
references: Lipids Health Dis. 2010 Jun 09;9:60
references: 20534152