Limits...
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.

Fan C, Liu X, Shen W, Deckelbaum RJ, Qi K - Nutr Metab (Lond) (2011)

Bottom Line: 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.For the CpG sites in the promoter regions of leptin-R, no methylation was found in any of the DIO or control groups.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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. qkm6@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

Regions of the mouse leptin, leptin-R and POMC promoters. The CG dinucleotides are underlined and letters (a to r) were assigned to each of the analyzed CGs. (A) The leptin promoter sequence with CpG islands spanning nucleotides -324 to -29. (B) The leptin-R promoter sequence with CpG islands spanning nucleotides -633 to -345. (C) The POMC promoter sequence with CpG islands spanning nucleotides -451 to -167.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3117679&req=5

Figure 1: Regions of the mouse leptin, leptin-R and POMC promoters. The CG dinucleotides are underlined and letters (a to r) were assigned to each of the analyzed CGs. (A) The leptin promoter sequence with CpG islands spanning nucleotides -324 to -29. (B) The leptin-R promoter sequence with CpG islands spanning nucleotides -633 to -345. (C) The POMC promoter sequence with CpG islands spanning nucleotides -451 to -167.

Mentions: The promoter regions of many eukaryotic genes contain stretches of CpG-rich sequences known as CpG islands. Percentage of Cs and Gs > 50%, ratio of observed to expected CG dinucleotides > 0.6 and size of CpG island sequence > 200 nucleotides were used to define CpG islands of gene promoters. As shown in Figure 1, the leptin promoter region examined covers nucleotides (nts) 29009221-29010220 and spans 16 CpGs within nts -324 to -29 (positions are given with respect to the transcription start site [TSS]). The leptin-R promoter region examined spans nts 101389512-101390511 and includes 18 CpGs within nts -633 to -345 (with respect to the TSS). The POMC promoter region examined spans nts 3954450-3955047 and includes 14 CpGs within nts -451 to -167 (with respect to the TSS). These sequence data have been submitted to the GenBank databases (http://www.ncbi.nlm.nih.gov) under accession number U18812, U46135 and NC_000078.5 respectively.


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.

Fan C, Liu X, Shen W, Deckelbaum RJ, Qi K - Nutr Metab (Lond) (2011)

Regions of the mouse leptin, leptin-R and POMC promoters. The CG dinucleotides are underlined and letters (a to r) were assigned to each of the analyzed CGs. (A) The leptin promoter sequence with CpG islands spanning nucleotides -324 to -29. (B) The leptin-R promoter sequence with CpG islands spanning nucleotides -633 to -345. (C) The POMC promoter sequence with CpG islands spanning nucleotides -451 to -167.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117679&req=5

Figure 1: Regions of the mouse leptin, leptin-R and POMC promoters. The CG dinucleotides are underlined and letters (a to r) were assigned to each of the analyzed CGs. (A) The leptin promoter sequence with CpG islands spanning nucleotides -324 to -29. (B) The leptin-R promoter sequence with CpG islands spanning nucleotides -633 to -345. (C) The POMC promoter sequence with CpG islands spanning nucleotides -451 to -167.
Mentions: The promoter regions of many eukaryotic genes contain stretches of CpG-rich sequences known as CpG islands. Percentage of Cs and Gs > 50%, ratio of observed to expected CG dinucleotides > 0.6 and size of CpG island sequence > 200 nucleotides were used to define CpG islands of gene promoters. As shown in Figure 1, the leptin promoter region examined covers nucleotides (nts) 29009221-29010220 and spans 16 CpGs within nts -324 to -29 (positions are given with respect to the transcription start site [TSS]). The leptin-R promoter region examined spans nts 101389512-101390511 and includes 18 CpGs within nts -633 to -345 (with respect to the TSS). The POMC promoter region examined spans nts 3954450-3955047 and includes 14 CpGs within nts -451 to -167 (with respect to the TSS). These sequence data have been submitted to the GenBank databases (http://www.ncbi.nlm.nih.gov) under accession number U18812, U46135 and NC_000078.5 respectively.

Bottom Line: 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.For the CpG sites in the promoter regions of leptin-R, no methylation was found in any of the DIO or control groups.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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. qkm6@hotmail.com.

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.

No MeSH data available.


Related in: MedlinePlus