The Time Point-Specific Effect of Beta-Adrenergic Blockade in Attenuating High Fat Diet-Induced Obesity and Bone Loss

We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12 weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for the first 12 weeks, followed by stratification into diet-based subgroups and another 12 weeks of treatment with vehicle or propranolol. Propranolol attenuated the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3 mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in femoral trabecular bone mineral density and bone architecture deterioration in Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise skeletal integrity. Taken together, propranolol attenuates HIGH-induced body weight increases while weight gain is in progress but not once obesity has already been established. HIGH feeding during the growth period results in compromised bone mass/architecture; which can be attenuated by propranolol administration during the growth period, but not by propranolol administration after obesity has already been established.