The dynamics of human bone marrow adipose tissue in response to feeding and fasting
Pouneh K. Fazeli, Miriam A. Bredella, Gisela Pachon-Peña, Wenxiu Zhao, Xun Zhang, Alexander T. Faje, Megi Resulaj, Sai P. Polineni, Tara M. Holmes, Hang Lee, Elizabeth K. O’Donnell, Ormond A. MacDougald, Mark C. Horowitz, Clifford J. Rosen, Anne Klibanski
Pouneh K. Fazeli, Miriam A. Bredella, Gisela Pachon-Peña, Wenxiu Zhao, Xun Zhang, Alexander T. Faje, Megi Resulaj, Sai P. Polineni, Tara M. Holmes, Hang Lee, Elizabeth K. O’Donnell, Ormond A. MacDougald, Mark C. Horowitz, Clifford J. Rosen, Anne Klibanski
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Clinical Research and Public Health Metabolism

The dynamics of human bone marrow adipose tissue in response to feeding and fasting

Abstract

BACKGROUND Adipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and responsive to hormonal and nutrient cues.METHODS In this study of healthy volunteers, we investigated how BMAT responds to acute nutrient changes, including analyses of endocrine determinants and paracrine factors from marrow aspirates. Study participants underwent a 10-day high-calorie protocol, followed by a 10-day fast.RESULTS We demonstrate (a) vertebral BMAT increased significantly during high-calorie feeding and fasting, suggesting BMAT may have different functions in states of caloric excess compared with caloric deprivation; (b) ghrelin, which decreased in response to high-calorie feeding and fasting, was inversely associated with changes in BMAT; and (c) in response to high-calorie feeding, resistin levels in the marrow sera, but not the circulation, rose significantly. In addition, TNF-α expression in marrow adipocytes increased with high-calorie feeding and decreased upon fasting.CONCLUSION High-calorie feeding, but not fasting, induces an immune response in bone marrow similar to what has been reported in peripheral adipose tissue. Understanding the immunomodulatory regulators in the marrow may provide further insight into the homeostatic function of this unique adipose tissue depot.FUNDING NIH grant R24 DK084970, Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH, award UL 1TR002541), and NIH grants P30 DK040561 and U19 AG060917S1.

Authors

Pouneh K. Fazeli, Miriam A. Bredella, Gisela Pachon-Peña, Wenxiu Zhao, Xun Zhang, Alexander T. Faje, Megi Resulaj, Sai P. Polineni, Tara M. Holmes, Hang Lee, Elizabeth K. O’Donnell, Ormond A. MacDougald, Mark C. Horowitz, Clifford J. Rosen, Anne Klibanski

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Figure 3

Changes in L4 vertebral BMAT, VAT, and SAT during the study in men.

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Changes in L4 vertebral BMAT, VAT, and SAT during the study in men. Chan...
Changes in L4 vertebral BMAT, VAT, and SAT during high-calorie feeding (A), during fasting (B), during 2-week stabilization period (C), and overall (D). Each cluster of 3 bars represents an individual male subject; subjects are listed in ascending order based on baseline BMI (the first cluster in each graph represents a male subject with a baseline BMI of 23.4 kg/m2; the last cluster in each graph represents a male subject with a baseline BMI of 27.8 kg/m2). During high-calorie feeding, L4 vertebral BMAT increased in 69.2% of men, VAT increased in 76.9% of men, and SAT increased in 100% of men (A). During fasting, L4 vertebral BMAT increased in 92.3% of men, VAT decreased in 76.9% of men, and SAT decreased in 84.6% of men (B). During the 2-week stabilization period, L4 vertebral BMAT decreased in 100% of men, VAT decreased in 84.6% of men, and SAT decreased in 38.5% of men (C). Compared with baseline, at the end of the study, L4 vertebral BMAT decreased in 46.2% of men, VAT decreased in 53.8% of men, and SAT decreased in 61.5% of men (D).