title: Expansion of Bone Marrow Adipose Tissue During Caloric Restriction Is Associated With Increased Circulating Glucocorticoids and Not With Hypoleptinemia.
abstract: Bone marrow adipose tissue (MAT) accounts for up to 70% of bone marrow volume in healthy adults and increases further in clinical conditions of altered skeletal or metabolic function. Perhaps most strikingly, and in stark contrast to white adipose tissue, MAT has been found to increase during caloric restriction (CR) in humans and many other species. Hypoleptinemia may drive MAT expansion during CR but this has not been demonstrated conclusively. Indeed, MAT formation and function are poorly understood; hence, the physiological and pathological roles of MAT remain elusive. We recently revealed that MAT contributes to hyperadiponectinemia and systemic adaptations to CR. To further these observations, we have now performed CR studies in rabbits to determine whether CR affects adiponectin production by MAT. Moderate or extensive CR decreased bone mass, white adipose tissue mass, and circulating leptin but, surprisingly, did not cause hyperadiponectinemia or MAT expansion. Although this unexpected finding limited our subsequent MAT characterization, it demonstrates that during CR, bone loss can occur independently of MAT expansion; increased MAT may be required for hyperadiponectinemia; and hypoleptinemia is not sufficient for MAT expansion. We further investigated this relationship in mice. In females, CR increased MAT without decreasing circulating leptin, suggesting that hypoleptinemia is also not necessary for MAT expansion. Finally, circulating glucocorticoids increased during CR in mice but not rabbits, suggesting that glucocorticoids might drive MAT expansion during CR. These observations provide insights into the causes and consequences of CR-associated MAT expansion, knowledge with potential relevance to health and disease.
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: William P
authors.initials: WP
authors.lastname: Cawthorn
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Scheller
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Sebastian D
authors.initials: SD
authors.lastname: Parlee
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: H An
authors.initials: HA
authors.lastname: Pham
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Learman
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Catherine M H
authors.initials: CM
authors.lastname: Redshaw
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sulston
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Burr
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Das
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Becky R
authors.initials: BR
authors.lastname: Simon
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mori
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bree
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schell
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
authors.affiliation: Departments of Molecular and Integrative Physiology (W.P.C., E.L.S., S.D.P., H.A.P., B.S.L., A.A.B., H.M., A.J.B., B.S., O.A.M.) and Internal Medicine (A.K.D., O.A.M.), and Program in Cellular and Molecular Biology (B.R.S., O.A.M.), University of Michigan Medical School, Ann Arbor, Michigan 48109; Musculoskeletal Research (W.P.C., V.K.), Lilly Research Laboratories, Indianapolis, Indiana 46285; and University/British Heart Foundation Centre for Cardiovascular Science (W.P.C., C.M.H.R., R.J.S.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom EH16 4TJ.
authors.forename: Ormond A
authors.initials: OA
authors.lastname: MacDougald
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015519:Bone Density; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D031204:Caloric Restriction / Q000009:adverse effects; D005260:Female; D005938:Glucocorticoids / Q000097:blood*; D020738:Leptin / Q000097:blood* / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011817:Rabbits
chemical_list: D005938:Glucocorticoids; D020738:Leptin