Abstract
BACKGROUNDAdipocytes 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.METHODSIn 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.RESULTSWe 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.CONCLUSIONHigh-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.FUNDINGNIH 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.
Highlights
Bone marrow adipose tissue (BMAT) is a major component of the bone marrow microenvironment, yet its function is not well understood
Individuals with anorexia nervosa, a psychiatric illness characterized by self-induced starvation and low body weight and a model of chronic starvation, have low levels of subcutaneous (SAT) and visceral adipose tissue (VAT) [1], BMAT levels are higher in girls and women with anorexia nervosa compared with normal-weight controls [2, 3]
We previously demonstrated that women with a history of anorexia nervosa who are at normal body weight have lower levels of BMAT
Summary
Bone marrow adipose tissue (BMAT) is a major component of the bone marrow microenvironment, yet its function is not well understood. Individuals with anorexia nervosa, a psychiatric illness characterized by self-induced starvation and low body weight and a model of chronic starvation, have low levels of subcutaneous (SAT) and visceral adipose tissue (VAT) [1], BMAT levels are higher in girls and women with anorexia nervosa compared with normal-weight controls [2, 3]. With more rapid weight changes (≤12 months), BMAT increases with weight gain and decreases with weight loss, suggesting that this adipose tissue depot behaves differently with subacute fluctuations in nutrient status and is a dynamic compartment [5]. 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
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