The adiponectin agonist AdipoRon accelerates osteoporosis development in two different models and modulates adipocyte differentiation

Osteoporosis is an increasing concern in the aging population worldwide, culminating in increased economic concerns and diminished quality of life. Similarly, disturbances of lipid metabolism and adipocytes accumulate more and more in western societies and need solutions. Adipocytes have recently attracted much interest in relation to their endocrine products, one of which is adiponectin, normally associated with beneficial effects on cardiovascular health, inflammation, and cancer. In this study, we have investigated the effect of AdipoRon, an adiponectin receptor agonist with reported anti-osteoclastic properties, on the development of osteoporosis in two different preclinical models. Contrasting to our initial hypothesis, AdipoRon treatment accelerated metabolic changes and bone loss in both models. However, AdipoRon rescued bone marrow adipocytes presence induced by glucocorticoids. Investigations on adipocyte differentiation revealed that AdipoRon potently changes adipocyte identity, by exerting opposite effects on adipocyte-gene induction depending on the time point and duration of stimulation. In conclusion, adipocyte-derived Adiponectin deserves further investigation as an autocrine mediator in musculoskeletal research.