A comparative study of the metabolic and skeletal response of C57BL/6J and C57BL/6N mice in a diet-induced model of type 2 diabetes

Type 2 diabetes mellitus (t2dm) represents a complex clinical scenario of altered energy metabolism and increased fracture incidence. the c57bl/6 mouse model of diet-induced obesity has been used to study the mechanisms by which altered glucose homeostasis affects bone mass and quality,but genetic variations in substrains of c57bl/6 may have confounded data interpretation. this study investigated the long-term metabolic and skeletal consequences of two commonly used c57bl/6 substrains to a high fat (hf) diet. male c57bl/6j,c57bl/6n,and the negative control strain,c3h/hej,mice were fed a control or hf diet for 24 wks. c57bl/6n mice on a hf diet demonstrated an increase in plasma insulin and blood glucose as early as 4 wk,whereas these responses were delayed in the c57bl/6j mice. the c57bl/6n mice exhibited more severe hepatic steatosis and inflammation. only the c57bl/6n mice lost significant trabecular bone in response to the high fat diet. the c3h/hej mice were protected from bone loss. the data show that c57bl/6j and c57bl/6n mice differ in their metabolic and skeletal response when fed a hf diet. these substrain differences should be considered when designing experiments and are likely to have implications on data interpretation and reproducibility. © 2015 elizabeth rendina-ruedy et al.