Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis fragility these remains ill-defined as present normal to high bone mineral density. With increasing cases intolerance T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized a fat diet (60%) administered developing male C57BL/6J mice had not reached maturity would over represent microarchitectural implications, skeletally mature better adult-onset the pre-diabetes phenotype. Two groups (8 week) (12 were placed onto either chow (NC) or (HFD) 10 weeks. Oral tolerance tests performed throughout study period. Long bones excised analysed ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry gene/protein expression analyses. HFD increased fasting blood significantly reduced both age by week 7 diets. strength, cortical trabecular indices mice, but only affected outcomes mice. Similar results reflected histomorphometry. Tibial gene revealed decreased formation groups, i.e., osteocalcin sclerostin RNA expression. In only, while led non-significant reduction runt-related transcription factor (Runx2) expression, this decrease became significant at protein level femora. Our mouse more accurately represents late-onset tolerance/pre-T2DM humans can be used uncover potential insights into mechanism patients.