1Although body mass index is positively associated with bone mineral density, suggesting obesity 2 is protective against fracture, elderly obese individuals experience greater fracture risk at certain 3 sites than non-obese peers, suggesting bone structural or material changes contribute to fragility. 4 Diet-induced obesity rodent studies have reported detrimental changes to bone microstructure and 5 some apparent-level material properties, but tissue-level material changes are not well understood. 6 Because adipose tissue is highly vascularized, and bone remodeling depends critically on 7 functional vascular supply, concurrent effects on osteovascular perfusion and structure may 8 provide insight about obesity-related bone fragility. This study aimed to determine the effects of 9 obesity on both tissue-level bone properties and osteovascular properties that could negatively 10 impact bone strength. Five-week-old male C57Bl/6J mice were fed either high fat diet (HFD) or 11 control fat diet (CFD) for 17 weeks and received daily treadmill exercise or remained sedentary 12 for eight weeks at ages 14-22 weeks. HFD negatively affected femur bending strength, with 18% 13 lower yield load than CFD. Although HFD negatively altered cancellous microstructure in the 14 distal femur, with 32% lower bone volume fraction than CFD, it did not affect cortical bone 15 geometry in the femoral metaphysis or diaphysis. HFD caused increased carbonate substitution 16 but had no effect on other composition metrics or apparent-or tissue-level material properties in 17 the femoral diaphysis. Exercise did not affect bone strength or microstructure but increased 18 endosteal mineralizing surface in the tibial diaphysis, mineral crystallinity and mineral-to-matrix 19 ratio in the femur, and blood supply to the proximal tibial metaphysis. HFD did not affect blood 20 supply in the tibia or 2D osteovascular structure in the distal femoral metaphysis, indicating that 21 HFD negatively affects cancellous bone without affecting osteovasculature. This study reveals that HFD negatively affected cancellous microstructure without affecting osteovascular structure, and 23 whole-bone strength without altering cortical geometry or material properties. 24 25 Keywords: 26 obesity, high fat diet, bone strength, material properties, exercise 27 28Over half of adults worldwide are overweight or obese. (1) Higher bone mineral density (BMD), a 29 primary determinant of bone strength (2) that is associated with decreased fracture incidence in 30 elderly men and women, (3,4) is associated with increasing body mass index (BMI) in both obese 31 and non-obese individuals. (4-7) However, increasing BMI in obese women is not as strongly 32 correlated with increasing BMD and estimated material strength compared to non-obese 33 women. (7,8) A meta-analysis reported that, despite having higher BMD, elderly obese individuals 34 experience higher fracture incidence at particular sites compared to non-obese individuals -obese 35 postmenopausal women have a h...