Short-term caloric restriction induced bone loss in both axial and appendicular bones by increasing adiponectin

Caloric restriction (CR) is well described and has received extensive attention for its multiple benefits, including longevity and stress resistance. However, some studies have shown that CR negatively influences bone, although a mechanism hasn't been provided. Adiponectin, an adipocyte-derived hormone, can affect bone metabolism by various pathways. To explore the role of adiponectin in short-term CR on bone, we tested the effect of short-term CR on limb bones (tibia and femur) and lumbar vertebral bodies of young C57BL/6 wild-type (WT) and adiponectin-deficient (Apn^-/- ) mice. Two dietary regimes, ad libitum (AL) and CR (70% of the AL diet), were used. Dietary restriction led to increased serum adiponectin in WT mice, while bone mineral density, bone microarchitecture, and biomechanical outcomes of limb bone and vertebrae were decreased. In contrast, bone length, microarchitecture, and biomechanical outcomes were not impaired after CR in Apn^-/- mice. Furthermore, CR increased adiponectin expression both in white adipose tissue and bone marrow adipose tissue in young WT mice. Histology analysis showed that expansion of bone marrow adipose tissue after CR in Apn^-/- mice was impaired compared with WT mice. These results suggest that increased adiponectin induced by short-term CR may negatively influence bones.