A Comparative Study of the Metabolic and Skeletal Response of C57BL6J and C57BL6N Mice in a Diet-Induced Model of Type 2 Diabetes

Abstract EN

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.