1. MUTATED G-PROTEIN-COUPLED RECEPTORGPR10IS RESPONSIBLE FOR THE HYPERPHAGIA/DYSLIPIDAEMIA/OBESITY LOCUS OFDmo1IN THE OLETF RAT.
- Author
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Watanabe, Takeshi K., Suzuki, Mikio, Yamasaki, Yuki, Okuno, Shiro, Hishigaki, Haretsugu, Ono, Toshihide, Oga, Keiko, Mizoguchi-Miyakita, Ayako, Tsuji, Atsushi, Kanemoto, Naohide, Wakitani, Shigeyuki, Takagi, Toshihisa, Nakamura, Yusuke, and Tanigami, Akira
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DIABETES ,OBESITY ,GENES ,PROTEINS ,LIGANDS (Biochemistry) ,RATS - Abstract
1. We have confirmed theDiabetes Mellitus OLETF type I(Dmo1) effect on hyperphagia, dyslipidaemia and obesity in the Otsuka Long-Evans Tokushima Fatty (OLETF) strain. The critical interval was narrowed down to 570 kb betweenD1Got258top162CA1by segregation analyses using congenic lines.2. Within the critical 570 kb region of theDmo1locus, we identified the G-protein-coupled receptor geneGPR10as the causative gene mutated in the OLETF strain. The ATG translation initiation codon ofGPR10is changed into ATA in this strain and, so, is unavailable for the initiation of translation.3. The GPR10 protein has a cognate ligand, namely prolactin-releasing peptide (PrRP). Centrally administered PrRP suppressed the food intake of congenic rats that have a Brown Norway derivedDmo1region (i.e. with wild-typeGPR10), but did not suppress that of the OLETF strain, indicating that GPR10 is without function and could explain hyperphagia in the OLETF strain.4. Moreover, when restricted in food volume to the same level consumed by the congenic strain, OLETF rats showed few differences in the parameters of dyslipidaemia and obesity compared with congenic strains.5. Taken together, these results demonstrate that the mutated GPR10 receptor is responsible for the hyperphagia leading to obesity and dyslipidaemia in the obese diabetic strain rat. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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