OR15-2 Bone Marrow Adipose Tissue as a Source of Serum Adiponectin: The ‘Adiponectin Paradox' Explained?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR15-Adipokine Action
Basic/Clinical
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:30 AM
Room 303 (Moscone Center)
William P Cawthorn*1, Erica L Scheller1, Brian S Learman1, David T Broome1, Sandra S Soliman1, Jenifer L DelProposto1, Carey N Lumeng1, Katherine A Gallagher2, Joshua D Miller2, Venkatesh Gary Krishnan3, Pouneh K Fazeli4, Anne Klibanski5, Mark C Horowitz6, Clifford J Rosen7 and Ormond A MacDougald1
1University of Michigan, Ann Arbor, MI, 2University of Michigan Hospital, Ann Arbor, MI, 3Eli Lilly and Company, Indianapolis, IN, 4Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 5Massachusetts General Hospital/Harvard Medical School, Boston, MA, 6Yale University School of Medicine, New Haven, CT, 7Maine Medical Center Research Institute, Scarborough, ME
The adipocyte-derived hormone adiponectin promotes insulin sensitivity, fat oxidation and anti-atherogenic effects, and serum adiponectin is widely used as a biomarker for insulin sensitivity and cardiovascular disease. Indeed, serum adiponectin levels are low in obese, insulin-resistant individuals but high in states of leanness such as caloric restriction (CR), type I diabetes or anorexia nervosa. These observations highlight the so-called ‘adiponectin paradox’: despite being produced exclusively by adipose tissue, serum adiponectin inversely correlates with % body fat. Even after extensive study of adiponectin following its discovery in 1995, the basis for this paradox is yet to be resolved.

The discovery of adiponectin preceded a surge of interest into white adipose tissue (WAT), which led to the current appreciation of WAT as a major endocrine organ. In contrast, research has largely neglected another adipose depot: bone marrow adipose tissue (MAT). Bone marrow adipocytes account for up to 70% of marrow volume in humans and, in contrast to WAT, MAT increases in states of leanness such as CR, type I diabetes or anorexia nervosa. Moreover, pharmacological agents such as thiazolidinediones or fibroblast growth factor-21 increase marrow adiposity. Notably, each of these conditions is also associated with increased serum adiponectin.

Based on these observations, we investigated the hypothesis that MAT is a major source of serum adiponectin. We found that, in rabbits or mice, adiponectin protein expression is markedly higher in MAT than in WAT. Although this was not consistently observed in human tissues, a subset of patients showed higher adiponectin secretion from MAT than from WAT. We next investigated if blocking MAT formation affects serum adiponectin levels. To do so we used Ocn-Wnt10b mice, in which the anti-adipogenic effector Wnt10b is transgenically expressed in bone. Although expression of adiponectin in WAT did not differ between Ocn-Wnt10b and control mice, Ocn-Wnt10b mice resisted the increases in MAT and serum adiponectin with CR. Finally, we found that total serum adiponectin negatively correlates with WAT mass or % body fat but positively correlates with MAT volume. These observations support the hypothesis that MAT expansion is required for increased serum adiponectin with CR, suggesting that MAT may be a major source of serum adiponectin. Thus, adiponectin production from MAT may account, at least in part, for the adiponectin paradox.

Disclosure: WPC: Researcher, Eli Lilly & Company. VGK: Employee, Eli Lilly & Company. OAM: Principal Investigator, Eli Lilly & Company. Nothing to Disclose: ELS, BSL, DTB, SSS, JLD, CNL, KAG, JDM, PKF, AK, MCH, CJR

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by grants from the National Institutes of Health (R24 DK092759 to O.A.M., A.K., M.C.H and C.J.R; RO1 DK090262 to C.N.L). W.P.C. was supported by a Lilly Innovation Fellowship Award and a Postdoctoral Research Fellowship from the Royal Commission for the Exhibition of 1851 (United Kingdom). D.T.B. and S.S.S. were supported by the UM Molecular & Integrative Physiology Department SURF program.