Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

Unlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids. In this study, we utilized a recently describ...

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Published in:	Frontiers in endocrinology (Lausanne) Vol. 15; p. 1397081
Main Authors:	Schill, Rebecca L, Visser, Jack, Ashby, Mariah L, Li, Ziru, Lewis, Kenneth T, Morales-Hernandez, Antonio, Hoose, Keegan S, Maung, Jessica N, Uranga, Romina M, Hariri, Hadla, Hermsmeyer, Isabel D K, Mori, Hiroyuki, MacDougald, Ormond A
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 03-06-2024
Subjects:	Adipocytes - metabolism Adipose Tissue - metabolism Adiposity - physiology Animals bone Bone and Bones - metabolism Bone Marrow - metabolism bone marrow adipose tissue (BMAT) Caloric Restriction caloric restriction (CR) Endocrinology Female glucocorticoid receptor (GR) glucocorticoids (GC) Hematopoiesis Male Metabolism, Inborn Errors Mice Mice, Inbred C57BL Mice, Knockout Receptors, Glucocorticoid - deficiency Receptors, Glucocorticoid - genetics Receptors, Glucocorticoid - metabolism hematopoiesis bone glucocorticoid receptor (GR) caloric restriction (CR) glucocorticoids (GC) bone marrow adipose tissue (BMAT)
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Summary:	Unlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids. In this study, we utilized a recently described mouse model ( ) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. ) whilst maintaining GR expression in other adipose depots. Mice lacking GR in BMAds ( ) and control mice ( ) were fed or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and μCT revealed no difference in BMAT accumulation between control or mice. Differences in BMAd size were not observed between and control mice. Interestingly, mice had decreased circulating white blood cell counts 4 h into the light cycle. In conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Biagio Palmisano, Sapienza University of Rome, Italy Edited by: Giuseppina Storlino, University of Foggia, Italy Robert Brommage, BoneGenomics, United States
ISSN:	1664-2392 1664-2392
DOI:	10.3389/fendo.2024.1397081