Minor gene effect of leptin receptor variant on the body weight in KK/Ta mice

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2006-09, Vol.8 (5), p.60721083724060-584
• Main Authors: Gohda, T., Tanimoto, M., Kaneko, S., Shibata, T., Funabiki, K., Horikoshi, S., Tomino, Y.
• Format: Article
• Language: English
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2006.00553.x

Objective: Leptin is an adipocyte-derived hormone involved in body weight regulation that acts through the leptin receptor. Previous studies exploring potential association between the leptin receptor (Lepr) variant and obesity have reported conflicting results. The objectives of the present study are to evaluate (1) whether the Lepr variant contributes to type 2 diabetes and its related disorders such as obesity and (2) whether the gene interaction between Lepr and Zn- alpha sub(2) glycoprotein1 (Azgp1) genes is recognized using genetically homogeneous type 2 diabetic KK-Ta mice. Methods: The levels of leptin (Lep) and Lepr mRNA in adipose tissues and brain were measured by relative quantitative RT-PCR. The levels of leptin protein in sera were measured by enzyme-linked immunosorbent assay. Genotyping of backcross mice was performed using a mismatch primer. Results: Leptin protein and its mRNA levels were increased in KK-Ta mice. Lepr mRNA levels of KK-Ta mice did not differ from those of BALB-c mice. Sequence analysis revealed that the coding region of Lep in KK-Ta mice was identical to that in BALB-c mice. Six nucleotide polymorphisms were observed in the coding region of Lepr. In KK-Ta x (BALB-c x KK-Ta) F1 backcross mice, the Lepr variant of KK-Ta mice failed to alter any of the variables of obesity except for body weight at 20 weeks of age. However, it enhanced the effect of Azgp1 on body weight. Conclusion: It is concluded that the Lepr variant contributes to obesity to some degree in KK-Ta mice.