Bone remodeling is energetically demanding process. Energy coming from nutrients present in the diet contributes to function of different cell type including osteoblasts, osteocytes and osteoclasts in bone marrow participating in bone homeostasis. With aging, obesity and osteoporosis the function of key building blocks, bone marrow stromal cells (BMSCs), changes towards higher accumulation of bone marrow adipose tissue (BMAT) and decreased bone mass, which is affected by diet and sex dimorphism. Men and women have unique nutritional needs based on physiological and hormonal changes across the life span. However, the exact molecular mechanisms behind these pathophysiological conditions in bone are not well-known. In this review, we focus on bone and BMAT physiology in men and women and how this approach has been taken by animal studies. Furthermore, we discuss the different diet interventions and impact on bone and BMAT in respect to sex differences. We also discuss the future perspective on precision nutrition with a consideration of sex-based differences which could bring better understanding of the diet intervention in bone health and weight management.

• Klíčová slova
• Nutrition, Diet composition, Bone, Bone marrow adiposity, Sex differences,
• MeSH
• adipozita * fyziologie   MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní dřeň * metabolismus   MeSH
• lidé MeSH
• nutriční stav MeSH
• pohlavní dimorfismus MeSH
• remodelace kosti fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Bone marrow stromal cells (BMSCs) play a significant role in bone metabolism as they can differentiate into osteoblasts, bone marrow adipocytes (BMAds), and chondrocytes. BMSCs chronically exposed to nutrient overload undergo adipogenic programming, resulting in bone marrow adipose tissue (BMAT) formation. BMAT is a fat depot transcriptionally, metabolically, and morphologically distinct from peripheral adipose depots. Reactive oxygen species (ROS) are elevated in obesity and serve as important signals directing BMSC fate. ROS produced by the NADPH oxidase (NOX) family of enzymes, such as NOX4, may be responsible for driving BMSC adipogenesis at the expense of osteogenic differentiation. The dual nature of ROS as both cellular signaling mediators and contributors to oxidative stress complicates their effects on bone metabolism. This review discusses the complex interplay between ROS and BMSC differentiation in the context of metabolic bone diseases.Special attention is paid to the role of NOX4-ROS in regulating cellular processes within the bone marrow microenvironment and potential target in metabolic bone diseases.

• Klíčová slova
• NADPH oxidase, ROS, bone fragility, bone marrow adipose tissue, bone marrow stromal cells, obesity, senescence,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Contrast-enhanced computed tomography offers a nondestructive approach to studying adipose tissue in 3D. Several contrast-enhancing staining agents (CESAs) have been explored, whereof osmium tetroxide (OsO4) is the most popular nowadays. However, due to the toxicity and volatility of the conventional OsO4, alternative CESAs with similar staining properties were desired. Hf-WD 1:2 POM and Hexabrix have proven effective for structural analysis of adipocytes using contrast-enhanced computed tomography but fail to provide chemical information. This study introduces isotonic Lugol's iodine (IL) as an alternative CESA for adipose tissue analysis, comparing its staining potential with Hf-WD 1:2 POM and Hexabrix in murine caudal vertebrae and bovine muscle tissue strips. Single and sequential staining protocols were compared to assess the maximization of information extraction from each sample. The study investigated interactions, distribution, and reactivity of iodine species towards biomolecules using simplified model systems and assesses the potential of the CESA to provide chemical information. (Bio)chemical analyses on whole tissues revealed that differences in adipocyte gray values post-IL staining were associated with chemical distinctions between bovine muscle tissue and murine caudal vertebrae. More specific, a difference in the degree of unsaturation of fatty acids was identified as a likely contributor, though not the sole determinant of gray value differences. This research sheds light on the potential of IL as a CESA, offering both structural and chemical insights into adipose tissue composition.

• Klíčová slova
• 3D histology, DICECT, Lugol’s iodine, adipocytes, adipose tissue, bone marrow, lipids/chemistry, muscle,
• MeSH
• barvení a značení metody   MeSH
• kontrastní látky * chemie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• počítačová rentgenová tomografie * metody   MeSH
• skot MeSH
• tuková tkáň * diagnostické zobrazování   metabolismus   MeSH
• tukové buňky cytologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kontrastní látky * MeSH

Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

• MeSH
• adipozita MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní dřeň * metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• obezita komplikace   prevence a kontrola   metabolismus   MeSH
• omega-3 mastné kyseliny * farmakologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• omega-3 mastné kyseliny * MeSH

OBJECTIVE: The use of thiazolidinediones (TZDs) as insulin sensitizers has been shown to have side effects including increased accumulation of bone marrow adipocytes (BMAds) associated with a higher fracture risk and bone loss. A novel TZD analog MSDC-0602K with low affinity to PPARγ has been developed to reduce adverse effects of TZD therapy. However, the effect of MSDC-0602K on bone phenotype and bone marrow mesenchymal stem cells (BM-MSCs) in relation to obesity has not been intensively studied yet. METHODS: Here, we investigated whether 8-week treatment with MSDC-0602K has a less detrimental effect on bone loss and BM-MSC properties in obese mice in comparison to first generation of TZDs, pioglitazone. Bone parameters (bone microstructure, bone marrow adiposity, bone strength) were examined by μCT and 3-point bending test. Primary BM-MSCs were isolated and measured for osteoblast and adipocyte differentiation. Cellular senescence, bioenergetic profiling, nutrient consumption and insulin signaling were also determined. RESULTS: The findings demonstrate that MSDC-0602K improved bone parameters along with increased proportion of smaller BMAds in tibia of obese mice when compared to pioglitazone. Further, primary BM-MSCs isolated from treated mice and human BM-MSCs revealed decreased adipocyte and higher osteoblast differentiation accompanied with less inflammatory and senescent phenotype induced by MSDC-0602K vs. pioglitazone. These changes were further reflected by increased glycolytic activity differently affecting glutamine and glucose cellular metabolism in MSDC-0602K-treated cells compared to pioglitazone, associated with higher osteogenesis. CONCLUSION: Our study provides novel insights into the action of MSDC-0602K in obese mice, characterized by the absence of detrimental effects on bone quality and BM-MSC metabolism when compared to classical TZDs and thus suggesting a potential therapeutical use of MSDC-0602K in both metabolic and bone diseases.

• Klíčová slova
• Bone marrow adiposity, Bone marrow mesenchymal stem cells, Bone microstructure, Obesity-induced bone fragility, Pioglitazone, Thiazolidinedione analog MSDC-0602K,
• MeSH
• antigen stromálních buněk kostní dřeně metabolismus   farmakologie   MeSH
• glukosa metabolismus   MeSH
• glutamin metabolismus   MeSH
• hypoglykemika farmakologie   MeSH
• inzulin metabolismus   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * metabolismus   MeSH
• myši obézní MeSH
• myši MeSH
• obezita farmakoterapie   metabolismus   MeSH
• pioglitazon metabolismus   farmakologie   MeSH
• PPAR gama metabolismus   MeSH
• spirosloučeniny MeSH
• thiazolidindiony * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 10-methyl spiro(4.5)dec-6-en-6-carboxylic acid MeSH Prohlížeč
• 2,4-thiazolidinedione MeSH Prohlížeč
• antigen stromálních buněk kostní dřeně MeSH
• glukosa MeSH
• glutamin MeSH
• hypoglykemika MeSH
• inzulin MeSH
• pioglitazon MeSH
• PPAR gama MeSH
• spirosloučeniny MeSH
• thiazolidindiony * MeSH