Osteoporosis is defined as a systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration leading to increased fracture risk. Osteoporosis incidence increases with age in both post-menopausal women and aging men. Among other important contributing factors to bone fragility observed in osteoporosis, that also affect the elderly population, are metabolic disturbances observed in obesity and Type 2 Diabetes (T2D). These metabolic complications are associated with impaired bone homeostasis and a higher fracture risk. Expansion of the Bone Marrow Adipose Tissue (BMAT), at the expense of decreased bone formation, is thought to be one of the key pathogenic mechanisms underlying osteoporosis and bone fragility in obesity and T2D. Our review provides a summary of mechanisms behind increased Bone Marrow Adiposity (BMA) during aging and highlights the pre-clinical and clinical studies connecting obesity and T2D, to BMA and bone fragility in aging osteoporotic women and men.

• Klíčová slova
• aging, bone fragility, bone marrow adiposity, obesity, osteoporosis, type 2 diabetes (T2D),
• MeSH
• adipozita MeSH
• diabetes mellitus 2. typu * metabolismus   MeSH
• fraktury kostí * metabolismus   MeSH
• kostní dřeň patologie   MeSH
• lidé MeSH
• obezita metabolismus   MeSH
• osteoporóza * patologie   MeSH
• senioři MeSH
• stárnutí MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

PURPOSE OF REVIEW: The goal of this review is to discuss the role of insulin signaling in bone marrow adipocyte formation, metabolic function, and its contribution to cellular senescence in relation to metabolic bone diseases. RECENT FINDINGS: Insulin signaling is an evolutionally conserved signaling pathway that plays a critical role in the regulation of metabolism and longevity. Bone is an insulin-responsive organ that plays a role in whole body energy metabolism. Metabolic disturbances associated with obesity and type 2 diabetes increase a risk of fragility fractures along with increased bone marrow adiposity. In obesity, there is impaired insulin signaling in peripheral tissues leading to insulin resistance. However, insulin signaling is maintained in bone marrow microenvironment leading to hypermetabolic state of bone marrow stromal (skeletal) stem cells associated with accelerated senescence and accumulation of bone marrow adipocytes in obesity. This review summarizes current findings on insulin signaling in bone marrow adipocytes and bone marrow stromal (skeletal) stem cells and its importance for bone and fat metabolism. Moreover, it points out to the existence of differences between bone marrow and peripheral fat metabolism which may be relevant for developing therapeutic strategies for treatment of metabolic bone diseases.

• Klíčová slova
• Bone marrow adipose tissue, Bone marrow mesenchymal stem cells, Insulin signaling, Marrow adiposity,
• MeSH
• adipogeneze MeSH
• buněčná diferenciace MeSH
• buňky kostní dřeně metabolismus   MeSH
• glukagonu podobný peptid 1 metabolismus   MeSH
• glukosa metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• inzulinová rezistence MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní dřeň metabolismus   MeSH
• lidé MeSH
• metabolické nemoci kostí metabolismus   MeSH
• mezenchymální kmenové buňky metabolismus   MeSH
• obezita metabolismus   MeSH
• parathormon metabolismus   MeSH
• protein 4 vázající insulinu podobné růstové faktory metabolismus   MeSH
• proteiny insulinového receptorového substrátu metabolismus   MeSH
• receptor inzulinu metabolismus   MeSH
• receptor pro konečné produkty pokročilé glykace metabolismus   MeSH
• stárnutí buněk * MeSH
• tuková tkáň metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• insulinu podobný růstový faktor I MeSH
• inzulin MeSH
• parathormon MeSH
• protein 4 vázající insulinu podobné růstové faktory MeSH
• proteiny insulinového receptorového substrátu MeSH
• receptor inzulinu MeSH
• receptor pro konečné produkty pokročilé glykace MeSH