Bae In-Seon, Kim Sang Hoon
Department of Animal Biotechnology and Environment, National Institute of Animal Science, Iseo-myeon, Wanju-gun 55365, Jeonbuk-do, Republic of Korea.
Department of Biology, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
Int J Mol Sci. 2025 Jun 23;26(13):6006. doi: 10.3390/ijms26136006.
The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice's body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome.
全球肥胖人口约占总人口的30%，且仍在持续增加。白色脂肪细胞在体内积聚用于能量储存，与肥胖相关。激活白色脂肪细胞褐变的机制是肥胖和代谢紊乱的一个有吸引力的治疗靶点。外泌体是纳米级生物囊泡，通过诸如微小RNA等货物的转移在细胞间通讯中发挥作用。尽管乳外泌体含有许多内源性微小RNA分子，但微小RNA在乳外泌体中的作用有限。因此，本研究的目的是探讨乳外泌体对白色脂肪细胞褐变的影响。将小鼠前脂肪细胞（3T3-L1）和人脂肪来源干细胞（hADSCs）进行分化并暴露于乳外泌体。与对照组相比，乳外泌体促进了3T3-L1细胞和hADSCs中产热基因的表达以及细胞线粒体能量代谢。此外，将乳外泌体口服给予高脂饮食喂养的小鼠。随着乳外泌体摄入量的增加，小鼠体重下降。乳外泌体还增加了小鼠脂肪组织中产热基因和线粒体相关基因的蛋白质水平。在3T3-L1细胞和hADSCs中过表达乳外泌体中丰富存在的miR-11987，导致产热基因表达增加和线粒体活性增强。我们的结果支持乳外泌体中牛特异性miR-11987促进白色脂肪细胞褐变。因此，乳外泌体和乳外泌体miR-11987可能对肥胖和代谢综合征具有重要的临床意义。
