Genetic, sex and diet effects on body weight and obesity in unique Berlin Fat Mouse inbred lines

Mouse lines long-term selected for high fatness offer the possibility to identify individual genes involved in the development of obesity. The Berlin Fat Mouse (BFM) line has been selected for low protein content and afterwards for high fatness. Three Berlin Fat Mouse Inbred (BFMI) lines, which are derivates of the selection line BFM, and an unselected control line (C57BL/6) were systematically phenotyped between three and 20 weeks. The body weights and body compositions were measured on a weekly basis. We demonstrated that the BFMI lines dispose of more body weight, body fat mass, and body lean mass than the control line B6 due to a better feed efficiency in these lines. In contrast to other growth selected mouse lines, the BFMI lines exhibited a general increase in body fat mass, but only a marginal increase in body lean mass. The three BFMI lines also showed line and sex-specific patterns and varied in their response to high-fat diet. The phenotypic differences between the BFMI lines can be traced back to different sets of fixed alleles contributing to fat accumulation and diet-induced obesity. Our results demonstrate that the genetically related Berlin Fat Mouse Inbred lines are novel models to study the genetic as well as the nutritional aspects of obesity