Galigniana Natalia M, Abdelhalim Mohamed, Collas Philippe, Sæther Thomas
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway.
Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0372 Oslo, Norway.
Nutrients. 2024 Dec 13;16(24):4310. doi: 10.3390/nu16244310.
Obesity and related metabolic disorders have reached epidemic levels, calling for diverse therapeutic strategies. Altering nutrient intake, timing and quantity by intermittent fasting seems to elicit beneficial health effects by modulating endocrine and cell signaling networks. This study explores the impact of cyclic nutrient availability in the form of every-other-day fasting (EODF) on human adipose stem cells (ASCs).
We subjected ASCs to repeated fasting/refeeding (F/R) cycles, mimicking low glucose/high fatty acid (LGHF) conditions, and assessed phenotypic and transcriptomic changes, lipid storage capacity, insulin sensitivity, and differentiation potential.
Four consecutive F/R cycles induced significant changes in adipogenic gene expression, with upregulation of and during fasting, and increased lipid storage in the ASCs. Upon differentiation, ASCs exposed to LGHF conditions retained a transient increase in lipid droplet size and altered fatty acid metabolism gene expression until day 9. However, these changes dissipated by day 15 of differentiation, suggesting a limited duration of fasting-induced transcriptional and adipogenic memory. Despite initial effects, ASCs showed resilience, returning to a physiological trajectory during differentiation, with respect to gene expression and lipid metabolism.
These findings suggest that the long-term effects of EODF on the ASC niche may be transient, emphasizing the ability of the adipose tissue to adapt and restore homeostasis.
肥胖及相关代谢紊乱已达到流行程度，需要多种治疗策略。通过间歇性禁食改变营养摄入的时间和量，似乎可通过调节内分泌和细胞信号网络产生有益的健康影响。本研究探讨隔日禁食（EODF）形式的周期性营养可利用性对人脂肪干细胞（ASC）的影响。
我们使ASC经历重复的禁食/再喂养（F/R）循环，模拟低葡萄糖/高脂肪（LGHF）条件，并评估表型和转录组变化、脂质储存能力、胰岛素敏感性和分化潜能。
连续四个F/R循环诱导脂肪生成基因表达发生显著变化，禁食期间 和 上调，且ASC中的脂质储存增加。在分化时，暴露于LGHF条件的ASC在第9天之前脂质滴大小持续短暂增加，脂肪酸代谢基因表达改变。然而，这些变化在分化第15天时消失，表明禁食诱导的转录和脂肪生成记忆持续时间有限。尽管有初始效应，但ASC在分化过程中在基因表达和脂质代谢方面表现出恢复力，回归到生理轨迹。
这些发现表明EODF对ASC生态位的长期影响可能是短暂的，强调了脂肪组织适应和恢复内稳态的能力。
