Foxk2 Enhances Adipogenic Differentiation by Relying on the Transcriptional Activation of Peroxisome Proliferator‐Activated Receptor Gamma

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(1)

Опубликована: Янв. 1, 2025

ABSTRACT Proper differentiation of bone marrow stromal cells (BMSCs) into adipocytes is crucial for maintaining skeletal homeostasis. However, the underlying regulatory mechanisms remain incompletely understood, posing a challenge treatment age‐related osteopenia and osteoporosis. Here, through comprehensive gene expression analysis during BMSC adipocytes, we identified forkhead transcription factor Foxk2 as key regulator this process. was significantly higher in inguinal epididymal white adipose tissues db/db mice compared to non‐obese db/m controls induced BMSCs, C3H/10 T1/2, ST2 following adipogenic stimulation. Overexpression promoted ST2, accompanied by increased lipogenic factors. Conversely, silencing inhibited differentiation. Moreover, also facilitated lipogenesis T1/2 cells. Adipogenic stimuli triggered nuclear translocation PI3‐kinase mTOR signalling pathways. Once nucleus, directly bound promoters Pparγ1 Pparγ2, thereby enhancing their transcriptional activity. Notably, PPARγ1 PPARγ2 reciprocally augmented activity promoter, indicating presence Foxk2‐PPARγ positive feedback loop that drives adipogenesis.

Язык: Английский

---

Marrow adiposity content and composition are not associated with incident fragility fractures in post-menopausal women

Journal of the Endocrine Society, Год журнала: 2025, Номер 9(4)

Опубликована: Фев. 24, 2025

Abstract Context Noninvasive measurement of bone marrow adipose tissue using magnetic resonance imaging and proton density fat fraction (PDFF) may enhance clinical fractures prediction in postmenopausal women. Objective This study aimed to assess the association between PDFF measurements fracture incidence. Methods A longitudinal was conducted. Postmenopausal women with recent osteoporotic (<12 months) osteoarthritis without were included. Lumbar spine proximal femur PDFFs measured at baseline water-fat (WFI) dual-energy x-ray absorptiometry scans. Clinical recorded during follow-up. Results Among 195 participants (mean age 67.4 ± 10.0 years, body mass index 27.2 5.9 kg/m²), (WFI-based) higher femur, particularly femoral head (90.0% 4.9%), compared lumbar (57.8% 9.6%). Over a mean follow-up period 37.2 11.6 months, 7 died, 29 (14.9%) experienced incident fractures, 1 lost The lack an WFI-based incidence demonstrated regardless region (hazard ratio [HR] = 0.95 [95% CI 0.67-1.35], P 0.77 spine, HR 1.07 0.71-1.63], 0.74 neck). Stepwise regression analysis did not alter these findings, variable “recent fractures” found be significantly associated fractures. Conclusion no evidence relationship Further studies are necessary involving larger cohorts longer periods.

Язык: Английский

---

Association of the Chinese visceral adiposity index with marrow adiposity in postmenopausal females

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Фев. 25, 2025

To investigate the relationship between Chinese visceral adiposity index (CVAI) and vertebral proton density fat fraction (PDFF). The study included 181 postmenopausal females including 53 normal bone mineral (BMD), 88 osteopenia, 40 osteoporosis. Vertebral marrow PDFF was measured using Fat Analysis & Calculation Technique imaging, BMD assessed via dual-energy X-ray absorptiometry. Bone turnover biomarkers lipid metabolism were evaluated. CVAI multivariable linear regression models, generalized additive threshold effect analysis. mean at lumbar spine increased, significantly decreased as quartiles of increased (P for trends <0.05). Multivariable analysis revealed a clear negative correlation (regression coefficient β = -0.251, 95% CI, -0.303 to -0.200; P < 0.001) after adjusting age, time since menopause, waist circumference, body mass index, physical activity, profiles. association with remained significant (β -0.202, -0.255 -0.149, even additional adjustment BMD. Further an L-shaped non-linear profiles, An inflection point identified 128.3, below which each one-unit increase in corresponded more substantial decrease -0.0055, CI: -0.0064 -0.0045; 0.001). However, above this point, unit not associated PDFF. exhibited nonlinear within suitable range, once crossed definite threshold, ceased increase. This finding suggests that moderate accumulation may enhance skeletal integrity, while excessive could potentially have detrimental effects.

Язык: Английский

---

General Principles of MRI of the Bone Marrow

Опубликована: Янв. 1, 2025

Язык: Английский

---

Lipid metabolism dysregulation for bone metastasis and its prevention

Expert Review of Anticancer Therapy, Год журнала: 2025, Номер unknown

Опубликована: Апрель 12, 2025

Bone metastasis often develops in advanced malignancies. Lipid metabolic dysregulation might play pivotal role cancer progression and subsequent deterioration of bone health at metastatic condition. In-depth understanding lipid reprogramming metastasized cells other stromal including marrow adipocyte (BMA) is an urgent need to develop effective therapy. This paper emphasizes providing overview multifaceted dysregulated lipids BMA association with by utilizing search terms metabolism, PubMed. study extends address mechanism linked metabolism various crucial genes (e.g. CSF-1, RANKL, NFkB NFATc1) involved metastasis. review examines therapeutic strategies targeting offer potential avenues disrupt lipid-driven On condition, molecules especially not only favors but also potentiate within cells. Distinct lipid-metabolism associated may act as biomarker, these challenging task for specific treatment. Curbing function resorption controlling drugs statins, omega-3 FA metformin) provide additional support curtail lipid-associated

Язык: Английский

---

Association of a Combined Body Mass Index and Regional Body Fat Percentage Metric With Fragility Fracture Risk: Evidence from a Large Observational Cohort

Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2025, Номер 16(2)

Опубликована: Апрель 1, 2025

Язык: Английский

---

Impact of Vitamin D Status and Nutrition on the Occurrence of Long Bone Fractures Due to Falls in Elderly Subjects in the Vojvodina Region of Serbia

Nutrients, Год журнала: 2024, Номер 16(16), С. 2702 - 2702

Опубликована: Авг. 14, 2024

Bone fractures are a significant public health issue among elderly subjects. This study examines the impact of diet and vitamin D status on risk long bone due to falls in subjects Vojvodina, Serbia. Conducted at University Clinical Center Vojvodina autumn/winter 2022–2023, included 210 >65 years: 105 (F: 80/M: 15) with controls. Groups were similar regarding age BMI. Dietary intakes (by two 24-h recalls) serum levels analyzed. The fracture group had significantly lower median daily intake (1.4 μg/day vs. 5.8 μg/day), calcium, energy, proteins, fats, fibers, dairy products, eggs, fish, edible fats/oils, higher sweets (p < 0.001 for all). Serum (40.0 nmol/L 76.0 nmol/L, p 0.001). Logistic regression identified as most important protective factor against fractures, ROC curve analysis indicated that > 50.5 decreased risk. Nutritional improvements (increased protein sources such dairy), increased sun exposure, routine supplementation during winter advised.

Язык: Английский

---

Relationship between adipocytes and hematological tumors in the bone marrow microenvironment: a literature review

Translational Cancer Research, Год журнала: 2024, Номер 13(10), С. 5691 - 5701

Опубликована: Окт. 1, 2024

The bone marrow microenvironment is closely related to normal hematopoiesis and hematologic tumors. Adipocytes are an important part of the microenvironment, in which they can release free fatty acids (FFAs) through lipolysis secrete adipocytokines, etc., participate hematopoiesis, occurrence treatment hematological In this review, we aim discuss how adipocytes (BMAs) influence proliferation, apoptosis, chemotherapy resistance cancer cells by reprogramming lipid metabolism secretion various adipocytokines.

Язык: Английский

---

Inflammatory Th17 cells are correlated with insulin resistance and erythrocyte parameters in overweight and obese children

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 14, 2024

Introduction Obesity is thought to be accompanied by chronic, low-grade, inflammation. The adipocytes are present in the subcutaneous and visceral fat tissue contribute bone marrow cell compartment. Therefore, it poses a question whether factors influencing adipocyte functions also have an impact on hematopoietic function of marrow. aim our study was evaluate association between erythrocyte parameters, proinflammatory Th17 lymphocytes, IR markers children with excessive body weight. Methods A total 27 overweight/obese 15 normal-weight aged 8–18 years were enrolled study. analysis included anthropometric measurements, evaluation frequency, carbohydrate metabolism parameters. Results In children, count ( p = 0.00002), hemoglobin (HGB) concentration 0.005), frequency cells 0.048) higher. Anthropometric parameters correlated as well all children. subset 0.01, r 0.38). Moreover, correlation fasting insulin (FI) 0.00005, 0.58), HOMA-IR QUICKI 0.000042, −0.59), HGB FI 0.037, 0.32), 0.37, 0.049, −0.31) found. group, 2 h after oral glucose tolerance test (OGTT) 0.04, 0.4), while OGTT 0.018, 0.45; 0.44, respectively). Conclusions Our confirmed that higher obesity positively resistance lymphocyte. Thus, can concluded reflect risk developing response chronic inflammation associated obesity. These simple, easily accessible, repeatable tests that, assessment obese patients, may herald metabolic syndrome serve helpful additional tool for assessing effectiveness treatment.

Язык: Английский

---

Immunotherapy in the Battle Against Bone Metastases: Mechanisms and Emerging Treatments

Pharmaceuticals, Год журнала: 2024, Номер 17(12), С. 1591 - 1591

Опубликована: Ноя. 26, 2024

Bone metastases are a prevalent complication in advanced cancers, particularly breast, prostate, and lung associated with severe skeletal-related events (SREs), including fractures, spinal cord compression, debilitating pain. Conventional bone-targeted treatments like bisphosphonates RANKL inhibitors (denosumab) reduce osteoclast-mediated bone resorption but do not directly impact tumor progression within the bone. This review focuses on examining growing potential of immunotherapy targeting unique challenges posed by metastases. Even though immune checkpoint (ICIs) have significantly changed cancer treatment, their appears limited because microenvironment’s immunosuppressive traits, which include high levels transforming growth factor-beta (TGFβ) immune-suppressing cells, such as regulatory T cells (Tregs) myeloid-derived suppressor (MDSCs). underscores investigation combined therapeutic approaches that might ease these difficulties, synergy agents aimed at bones (denosumab, bisphosphonates), chemotherapy, radiotherapy, well combination different immunotherapeutic methods, CAR T-cell therapy. provides comprehensive analysis preclinical studies clinical trials show synergistic approaches, aim to both enhance responses mitigate destruction. By offering an in-depth exploration how strategies can be tailored microenvironment, this need for personalized treatment approaches. The findings emphasize urgent further research into overcoming evasion metastases, goal improving patient survival quality life.

Язык: Английский

---