The Time Point-Specific Effect of Beta-Adrenergic Blockade in Attenuating High Fat Diet-Induced Obesity and Bone Loss
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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.
KeywordsPropranolol Beta-adrenergic receptor blockade Obesity Bone loss High fat diet
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (2011-0016548, 2017R1A2B1006203).
KB and J‑HB designed the study. KB prepared the first draft of the paper. KB, JK, JL, and MK contributed to the experimental work. KB conducted the statistical analysis of the data. KB and J‑HB revised the paper critically for intellectual content and approved the final version. J‑HB is guarantor. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.
Compliance with Ethical Standards
Conflict of interest
Kyunghwa Baek, Jiho Kang, Jinu Lee, Min Kim and Jeong‑Hwa Baek declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Human and Animal Rights
All procedures performed in studies involving animals were in accordance with the ethical standards of Seoul National University Institutional Animal Care and Use Committee (SNU-110531-2).
Informed consent was obtained from all the authors of this manuscript.
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