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Leptin gene promoter DNA methylation in WNIN obese mutant rats

Rajender Rao Kalashikam12*, Padmavathi JN Inagadapa2, Anju Elizabeth Thomas2, Sugeetha Jeyapal2, Nappan Veettil Giridharan1 and Manchala Raghunath2

Author Affiliations

1 Molecular Genetics, National Center for Laboratory Animal Sciences, National Institute of Nutrition, Jamai Osmania P O, Hyderabad 500 007, India

2 Division of Endocrinology and Metabolism, National Institute of Nutrition, Hyderabad, India

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Lipids in Health and Disease 2014, 13:25  doi:10.1186/1476-511X-13-25

Published: 5 February 2014



Obesity has become an epidemic in worldwide population. Leptin gene defect could be one of the causes for obesity. Two mutant obese rats WNIN/Ob and WNIN/GROb, isolated at National Centre for Laboratory Animal Sciences (NCLAS), Hyderabad, India, were found to be leptin resistant. The present study aims to understand the regulatory mechanisms underlying the resistance by promoter DNA methylation of leptin gene in these mutant obese rats.


Male obese mutant homozygous, carrier and heterozygous rats of WNIN/Ob and WNIN/GROb strain of 6 months old were studied to check the leptin gene expression (RT-PCR) and promoter DNA methylation (MassARRAY Compact system, SEQUENOM) of leptin gene by invivo and insilico approach.


Homozygous WNIN/Ob and WNIN/GROb showed significantly higher leptin gene expression compared to carrier and lean counterparts. Leptin gene promoter DNA sequence region was analyzed ranging from transcription start site (TSS) to-550 bp length and found four CpGs in this sequence among them only three CpG loci (-309, -481, -502) were methylated in these WNIN mutant rat phenotypes.


The increased percentage of methylation in WNIN mutant lean and carrier phenotypes is positively correlated with transcription levels. Thus genetic variation may have effect on methylation percentages and subsequently on the regulation of leptin gene expression which may lead to obesity in these obese mutant rat strains.

Leptin expression; Promoter DNA methylation; Insilico analysis; Obesity; WNIN