Obesity is a major risk factor for the onset of
type 2 diabetes; however, little is known about the gene(s) involved. Therefore, we developed new animal models of
obesity to search for diabetogenic genes associated with
obesity. We generated double congenic rat strains with a hyperglycaemic quantitative trait locus (QTL) derived from the Otsuka Long-Evans Tokushima Fatty rat and a fa/fa (Lepr-/-) locus derived from the Zucker Fatty rat; phenotypic analysis for plasma
glucose and
insulin levels and
RNA and
protein levels were determined using reverse transcription quantitative PCR and Western blotting analyses, respectively. The double congenic strain F344-fa-nidd2 (Lepr-/- and Nidd2/of) exhibited significantly higher
glucose levels and significantly lower hypoglycaemic response to
insulin than the obese control strain F344-fa (Lepr-/-). These phenotypes were clearly observed in the obese strains but not in the lean strains. These results indicate that the Nidd2/of locus harbours a diabetogenic gene associated with
obesity. We measured the expression of 60 genes in the Nidd2/of QTL region between the strains and found that the
mRNA expression levels of five genes were significantly different between the strains under the condition of
obesity. However, three of the five genes were differentially expressed in both obese and lean rats, indicating that these genes are not specific for the condition of
obesity. Conversely, the other two genes,
coenzyme Q2 (Coq2) and placenta-specific 8 (Plac8), were differentially expressed only in the obese rats, suggesting that these two genes are candidates for the onset of
type 2 diabetes associated with
obesity in rats.