Summary The adipocyte-derived hormone adiponectin promotes metabolic and cardiovascular health. Circulating adiponectin increases in lean states such as caloric restriction (CR), but the reasons for this paradox remain unclear. Unlike white adipose tissue (WAT), bone marrow adipose tissue (MAT) increases during CR, and both MAT and serum adiponectin increase in many other clinical conditions. Thus, we investigated whether MAT contributes to circulating adiponectin. We find that adiponectin secretion is greater from MAT than WAT. Notably, specific inhibition of MAT formation in mice results in decreased circulating adiponectin during CR despite unaltered adiponectin expression in WAT. Inhibiting MAT formation also alters skeletal muscle adaptation to CR, suggesting that MAT exerts systemic effects. Finally, we reveal that both MAT and serum adiponectin increase during cancer therapy in humans. These observations identify MAT as an endocrine organ that contributes significantly to increased serum adiponectin during CR and perhaps in other adverse states.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health (R24 DK092759 to O.A.M., A.K., M.C.H., and C.J.R.; R01 DK62876 to O.A.M.; K99-DE-024178 to E.L.S.; R01 DK090262 to C.N.L.; 1R03AR055333 and 1K12-HD055887 to S.K.H.; P30 DK089503 to the Michigan Nutrition Obesity Research Center). S.K.H. is also supported by the Translational Science Institute of University of Minnesota (8UL1TR0001114). O.A.M. holds a Fulbright Scholar Award. W.P.C. holds a Lilly Innovation Fellowship Award and previously a Postdoctoral Research Fellowship from the Royal Commission for the Exhibition of 1851. H.M. was supported by a mentor-based postdoctoral fellowship from the American Diabetes Association. D.T.B. and S.S.S. were supported by the University of Michigan Molecular & Integrative Physiology Department SURF program. W.P.C. holds a postdoctoral fellowship funded by Eli Lilly and Company; V.K. is employed by Eli Lilly and Company; O.A.M. holds stock in MRK and ESRX and has received research funding from Eli Lilly and Company. E.L.S. and O.A.M. have received research funding from Biomet Biologics. A.K. has received research funding from Rhythm Pharmaceuticals.