Costa Samantha N, Pachón-Peña Gisela, Dragon Julie, Tighe Scott, Vary Calvin, Fazeli Pouneh K, Bredella Miriam A, Rosen Clifford J
Center of Molecular Medicine, MaineHealth Institute for Research, Scarborough, ME, United States.
Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, United States.
Front Endocrinol (Lausanne). 2025 Jun 16;16:1591280. doi: 10.3389/fendo.2025.1591280. eCollection 2025.
Expansion of bone marrow (BM) adipocytes has been linked to nutritional pressures, suggesting that BM is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here, we investigated BM metabolism in response to acute overnutrition (high calorie diet; HCD) and calorie deprivation (fasting). Participants underwent a 10-day HCD followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting. BM adipocytes and sera were collected before and after each dietary intervention for each participant. Using comprehensive and integrated analyses, we characterized nutritional influences on BM adiposity. BM adipocytes after HCD showed an upregulation of , the transcription factor that controls the development of Tregs, which are critical in reducing inflammatory immune responses. After fasting, BM adipocytes had an upregulation of inflammatory genes (, , and . Proteomic analysis after HCD showed that BM serum had an upregulation of proteins related to an inflammatory/complement pathway. After fasting, in the BM serum, there was a significant downregulation of inflammatory/complement pathway proteins. Despite both interventions causing BM adipose tissue expansion, the mechanism for adipogenesis appears to be dependent on nutrient availability. After HCD, lipid-mediated signaling and lipid storage, and lipid droplet biogenesis were significantly downregulated. In contrast, after fasting, lipid-mediated signaling and lipid storage, and lipid droplet biogenesis were significantly upregulated. Overall, our results demonstrate key differences in inflammatory response and lipid metabolism between HCD and fasting, despite a nearly identical BM adipose phenotype. Further analyses are needed to understand the effects nutritional pressures have on BM adipogenesis and immune responses.
骨髓（BM）脂肪细胞的扩张与营养压力有关，这表明骨髓是一个动态的隔间，它会对全身营养可用性的波动做出反应，以调节骨生成和造血作用。在这里，我们研究了骨髓代谢对急性营养过剩（高热量饮食；HCD）和热量剥夺（禁食）的反应。参与者先进行了为期10天的高热量饮食，随后有两周的随意饮食间隔，然后再进行10天的禁食。在每次饮食干预前后，为每位参与者采集骨髓脂肪细胞和血清。通过全面和综合分析，我们确定了营养对骨髓脂肪含量的影响。高热量饮食后的骨髓脂肪细胞显示出控制调节性T细胞（Tregs）发育的转录因子上调，调节性T细胞在减少炎症免疫反应中至关重要。禁食后，骨髓脂肪细胞的炎症基因（、和）上调。高热量饮食后的蛋白质组分析表明，骨髓血清中与炎症/补体途径相关的蛋白质上调。禁食后，骨髓血清中炎症/补体途径蛋白质显著下调。尽管两种干预都导致骨髓脂肪组织扩张，但脂肪生成的机制似乎取决于营养可用性。高热量饮食后，脂质介导的信号传导、脂质储存和脂滴生物合成显著下调。相反，禁食后，脂质介导的信号传导、脂质储存和脂滴生物合成显著上调。总体而言，我们的结果表明，尽管骨髓脂肪表型几乎相同，但高热量饮食和禁食在炎症反应和脂质代谢方面存在关键差异。需要进一步分析以了解营养压力对骨髓脂肪生成和免疫反应的影响。
