7216 Absence Of Weight Gain In C57Bl/67 Female Mice On A High-Fat Diet Protects The Skeleton From Bone Loss

Abstract Disclosure: C. McAndrews: None. C. Chlebek: None. S. Costa: None. C.J. Rosen: None. Background: Obesity is associated with both systemic metabolic changes that increase the risk of comorbidities and reduced bone quality that increases the risk of fracture. The effects of high-fat diet consumption have been well studied in preclinical models where high-fat diet-feeding induces obesity, but there have been no studies to investigate the effects of high-fat diet-feeding in animals that do not become obese. Therefore, we characterized components of systemic metabolism and bone mineral content in non-obese C57Bl/6J mice that were fed a high-fat diet. Methods: Female C57Bl/6J mice aged 8 weeks received either a high-fat (60% kcal fat, n = 31) or control (10% kcal fat, n = 17) diet for 12 weeks. Body composition, areal bone mineral density (BMD) and bone mineral composition (BMC) were assessed after the feeding period using dual energy x-ray absorptiometry (Faxitron UltraFocus-DXA). Glucose (GTT) and insulin (ITT) tolerance testing were performed at the conclusion of the study. Changes in body weight were calculated as the difference between baseline and experiment end. High-fat diet-fed animals were classified as obese (HFD-O, n = 24) if they weighed more than 25 g or had greater than 25% body fat as evaluated via DXA, and were otherwise considered non-obese (HFD-NO, n = 7). In a small subset of animals, subcutaneous inguinal fat pads were harvested and weighed (n=5-7/group). Differences between groups were assessed with one-way ANOVAs and Tukey post-hoc analyses. Results: HFD-O mice weighed more than HFD-NO and control animals, whereas the body weights of HFD-NO mice were not significantly different from control (p < 0.001). Fat percent was increased in HFD-O mice compared to HFD-NO and control animals (p < 0.001). Subcutaneous inguinal fat mass was increased in both HFD-O and HFD-NO mice compared to control (p < 0.001). Fasting blood glucose did not significantly differ between groups. Glucose tolerance was worsened in both HFD-O and HFD-NO mice compared to control (p < 0.001), but there were no significant differences in insulin tolerance between groups. BMD was decreased in HFD-O mice compared to HFD-NO and control animals (p < 0.001). DISCUSSION: The consumption of a high-fat diet in mice induces deleterious metabolic changes irrespective of weight gain. However, high-fat diet-induced bone loss does not occur in the absence of weight gain. These findings suggest that certain adipokines derived from larger adipose depots may drive high-fat diet-induced bone loss and warrant further investigation. Acknowledgements: This work was supported by the 2023 Endocrine Society Research Experiences for Graduate and Medical Students (REGMS) Program. Presentation: 6/1/2024