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Background: Increased levels of bone marrow adipose tissue (BMAT) are negatively associated with skeletal health and hematopoiesis. BMAT is known to increase with age; however, the effect of long-term weight loss on BMAT is still unknown., Objective: In this study, we examined BMAT response to lifestyle-induced weight loss in 138 participants (mean age 48 y; mean body mass index 31 kg/m 2 ), who participated in the CENTRAL-MRI trial., Methods: Participants were randomized for dietary intervention of low-fat or low-carb, with or without physical activity. Magnetic resonance imaging (MRI) was used to quantify BMAT and other fat depots at baseline, six and eighteen months of intervention. Blood biomarkers were also measured at the same time points., Results: At baseline, the L3 vertebrae BMAT is positively associated with age, HDL cholesterol, HbA1c and adiponectin; but not with other fat depots or other metabolic markers tested. Following six months of dietary intervention, the L3 BMAT declined by an average of 3.1 %, followed by a return to baseline after eighteen months (p < 0.001 and p = 0.189 compared to baseline, respectively). The decrease of BMAT during the first six months was associated with a decrease in waist circumference, cholesterol, proximal-femur BMAT, and superficial subcutaneous adipose tissue (SAT), as well as with younger age. Nevertheless, BMAT changes did not correlate with changes in other fat depots., Conclusions: We conclude that physiological weight loss can transiently reduce BMAT in adults, and this effect is more prominent in younger adults. Our findings suggest that BMAT storage and dynamics are largely independent of other fat depots or cardio-metabolic risk markers, highlighting its unique functions., Competing Interests: Conflict of interest Authors declare no conflicts., (Copyright © 2023 Elsevier Inc. All rights reserved.)