Bone marrow adipose tissue (BMAT) is a specialized fat depot located within the medullary cavities of long bones, accounting for over 10% of total body fat in humans. Once considered a passive filler, BMAT is now recognized as a metabolically active endocrine organ that influences bone homeostasis and systemic metabolism. Unlike white or brown adipose tissue, BMAT derives from bone marrow mesenchymal stromal cells and resides in close proximity to hematopoietic and stromal niche cells. Notably, BMAT expands in both obesity and under caloric restriction, highlighting its distinct regulatory mechanisms. Emerging evidence suggests that BMAT undergoes context-specific remodeling during metabolic stress, with obesity-associated BMAT acquiring inflammatory and metabolically dysfunctional features, whereas formation of energy deficit-associated BMAT may reflect adaptive stress responses within the bone marrow niche. This review synthesizes recent advances in BMAT heterogeneity, metabolic programming, and BMAT-hematopoietic interactions across states of nutrient excess and energy deficit.
Glucocorticoids are essential steroid hormones whose excess – whether from therapeutic use or endogenous overproduction – causes significant bone loss and fracture risk. In bone, glucocorticoids act directly on osteoblasts, osteocytes, and osteoclasts via the glucocorticoid receptor and indirectly through bone marrow adipose tissue and shared mesenchymal progenitors. An important mechanism involves suppression of canonical Wnt/β-catenin signaling, which reduces osteogenesis and increases marrow adiposity. Several pharmacological and plant-derived compounds with therapeutic promise target Wnt and other glucocorticoid-regulated signaling pathways. Emerging evidence highlights intermediary and potential therapeutic roles for niche-derived extracellular vesicles in bone loss associated with glucocorticoids. Comparing results between studies is complicated by underreporting of environmental and biological variables that may interact with glucocorticoids to affect bone or the marrow niche, which underscores the need for greater methodological rigor in preclinical studies.
Transgender and gender-diverse (TGD) individuals face unique cardiometabolic risks shaped by hormone exposure, social determinants, and structural inequities. This review summarizes the recent advances in understanding how gender-affirming hormone therapy affects cardiovascular outcomes, lipid metabolism, insulin sensitivity, and body composition. Estrogen therapy in transfeminine people may increase thrombotic risk and alter lipid profiles, while testosterone therapy in transmasculine individuals affects high-density lipoprotein (HDL) and hematocrit. Data in adolescents and individuals on puberty blockers remain limited. Social stressors, healthcare discrimination, and systemic barriers further compound risk. Methodologic challenges, including inadequate cohort designs and binary reference norms hinder progress. Further research must prioritize inclusive, longitudinal studies that integrate clinical and social exposures to improve cardiometabolic care for TGD populations.
Iron metabolism has emerged as a key regulator of immune function influencing both systemic and cellular metabolism. During physiological stress or infection, immune cells must tightly regulate iron availability and anabolic metabolism, ensuring sufficient supply to support immune effector functions while simultaneously restricting access to invading pathogens. This review examines the critical dependence of immunometabolism on efficient iron homeostasis, highlighting the bidirectional interplay between these processes, from the citric acid cycle, oxidative phosphorylation and glycolysis to the pentose phosphate pathway and fatty acid oxidation. We further discuss how disruptions in iron handling and immunometabolism contribute to health and disease in the lung and consider how these insights may inform novel therapeutic strategies.
