7943 In Obese C57Bl6 Male Mice, Weight Loss due to Caloric Restriction Reduced Bone Morphology but Improved Components of Systemic Metabolism
Authors: Chlebek Carolyn , McAndrews Casey , Costa Samantha N , Rosen Clifford J 
Published: October 2024

Disclosure: C. Chlebek: None. C. McAndrews: None. S.N. Costa: None. C.J. Rosen: None.

Obesity and calorie restriction individually alter systemic cellular metabolism and affect musculoskeletal tissue health. Obesity reduces trabecular and cortical bone quality. Clinically, obese patients are advised to lose weight, despite the negative effects of calorie restriction on bone in nonobese preclinical models. Little is known about bone quality following weight loss in obese preclinical models. We hypothesized that in obese models, caloric restriction would further worsen bone quality. To induce obesity, male C57Bl6 mice (8 weeks old) received 60% high fat diet for 12 weeks (high fat feeding phase). Following obesity induction, the HFD-CR group was acclimated to control low fat diet for 2 wks and then underwent 30% caloric restriction for 8 wks (caloric restriction feeding phase). The HFD group received 60% kcal high fat diet from ages 8 to 30 wks. LFD mice received control low fat 10% kcal diet for the study duration. Mice were euthanized at 30 wks of age. Body weight, body composition, and bone mineral density were recorded at baseline and at the end of each diet. Glucose and insulin tolerance were recorded at the end of the high fat and caloric restriction feeding phases. At euthanasia, cortical and trabecular bone morphology (µCT) were assessed.Adverse metabolic parameters worsened with high fat feeding but improved by caloric restriction. Compared to LFD animals, HFD and HFD-CR mice gained body weight, fat mass, and lean mass during the high fat feeding phase. After the caloric restriction feeding phase, body weight, fat mass, and lean mass were reduced in HFD-CR compared to both HFD and LFD controls (p &lt; 0.0001). After 12 weeks of high fat feeding, glucose and insulin tolerance were reduced in HFD and HFD-CR mice compared to LFD (p &lt; 0.0001). Caloric restriction improved both glucose and insulin tolerance in HFD-CR mice compared to both HFD and LFD animals (p &lt; 0.0001). Caloric restriction improved areal bone mineral density, but at euthanasia, HFD-CR mice had worse bone morphology compared to LFD or HFD animals. Although areal bone mineral density (aBMD) was reduced by the high fat feeding phase, HFD-CR and LFD aBMD was not different at the end of the study (p &lt; 0.0001). At euthanasia, HFD-CR mice had reduced cortical area and cortical thickness (p &lt; 0.05). Marrow area and moment of inertia were not different between diets. Compared to LFD, both HFD and HFD-CR mice had reduced tibial bone volume fraction (p &lt; 0.05). HFD-CR animals had smaller trabecular thickness (p &lt; 0.05) and greater trabecular number (p &lt; 0.01) compared to HFD mice. Despite improvements in components of systemic metabolism, caloric restriction in obese preclinical models reduced bone morphology in both trabecular and cortical compartments. This work will improve our understanding of the musculoskeletal system following caloric restriction in obese models and will aid in nutritional counseling for obese patients.

Presentation: 6/1/2024