1677-P: Identification of a Chromosome 1 Substitution Line B6-Chr1YP1 as a Novel Obesity Model via Phenotyping Screening

Obesity, a pandemic of modern world, is a chronic disease that seriously affects human health. The causes of obesity are complicated, including environmental factors and genetic factors. Due to the fact that traditional animal models cannot fully mimic obesity in human, new animal models are urgently needed for basic drug research on obesity. Previous studies have demonstrated that the genomic diversity of the wild mice chromosome 1 substitution lines was significantly different from that of laboratory mice, suggesting that it might be accompanied by phenotypic diversity. We firstly screened the obesity-related phenotype of chromosome 1 substitution lines and found that the male chow-diet-fed B6-Chr1YP1 mice showed severe obesity-related phenotypes in body weight, lipid metabolism and liver lesions. Compared with C57BL/6J mice, B6-Chr1YP1 showed much more severe obesity-related phenotypes when fed with high-fat-diet. Furthermore, we evaluated efficacy effects of Tirzepatide and MGL-3196 in B6-Chr1YP1 mice, and obesity-related phenotypes were significantly rescued. Taken together, male B6-Chr1YP1 mice could serve as a novel, polygenic interaction-based obesity and hyperlipidemia model. This study could provide a novel animal model for accurate clinical diagnosis and precise medicine of obesity and hyperlipidemia.