AdipoRon Modulate Aged Bone, Adipocyte Differentiation and Metabolism

Objectives: This study aims to investigate the effects of the adiponectin receptor agonist AdipoRon on osteogenic differentiation in the femur, as well as on the differentiation of brown adipose tissue, inguinal white adipose tissue, and intrabone adipose tissue in aged mice, and to elucidate the potential mechanisms underlying its actions.
Methods: Aged and young C57 mice received AdipoRon at varying doses to study its metabolic and body weight impacts. Tests included
glucose/insulin tolerance and cold exposure for thermoregulation. Samples from femur, blood, WAT, and BAT were analyzed for
bone density, fat content, and gene expression related to adipogenesis and metabolism. AdipoRon effects on adipogenic
differentiation and cellular metabolism were also assessed.
Results: Aged C57 mice treated with AdipoRon showed increased WAT adipogenesis and decreased BAT adipogenesis compared to
controls, while young mice showed the reverse. qRT-PCR indicated AdipoRon promoted BAT adipogenesis and metabolic
gene expression in young mice, particularly ucp1, but suppressed WAT metabolic genes in young and enhanced them in aged mice. AdipoRon reduced aged WAT cell respiration and ATP production, affected bone density and fat content differently in
aged and young mice, and influenced bone formation. It improved aged mice's thermoregulation and increased young mice's activity and energy expenditure, but decreased these in aged mice.
Conclusions: In summary, AdipoRon differentially affects osteogenic and adipogenic processes and thermogenic metabolism in young
versus aged C57 mice, enhancing bone and energy metabolism in young mice while suppressing WAT differentiation. On the contrary, AdipoRon had opposite effects on aged mice, which might be related to the increased WAT and decreased BAT in aged mice