Alessio Nicola, Squillaro Tiziana, Monda Vincenzo, Peluso Gianfranco, Monda Marcellino, Melone Mariarosa Ab, Galderisi Umberto, Di Bernardo Giovanni
Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania Luigi Vanvitelli, Naples 80138, Italy.
Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, 2 Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, Naples 80138, Italy.
World J Stem Cells. 2019 Mar 26;11(3):180-195. doi: 10.4252/wjsc.v11.i3.180.
Research on physiopathology of obesity may receive new hints from studies on skinny people (SP). These are individuals who show a poor or null gaining of body weight, in spite of high-calorie intake, by far exceeding the body requirements.
To evaluate how circulating factors present in the SP sera may affect adipogenesis of mesenchymal stromal cells (MSCs).
We isolated MSCs from bone marrow of healthy donors with both normal body mass index (BMI) and caloric consumption. MSC cultures were primed with sera collected from SP or normal people (NP). Then biomolecular assays were performed to evaluate effect on proliferation, apoptosis, senescence, cell commitment, and differentiation.
SP priming affected adipocyte cell commitment and reduced spontaneous adipogenesis. Moreover, an in-depth analysis of exogenous-induced adipocyte differentiation showed striking differences between differentiation in SP-primed samples compared with NP ones. In adipocytes from SP cultures we observed a reduced size of lipid droplets, an increased expression of adipose triglyceride lipase, along with high mitochondria content and ability to produce ATP in starvation condition. These data and the expression of UCP1 protein, indicated that SP pretreatment produced a bias toward brown adipocyte differentiation.
Our data suggest that sera from SP may promote brown adipogenesis rather that white adipocyte differentiation. This finding could explain why SP present normal body composition in spite of an excess of caloric intake. We hypothesize that some circulating components present in the blood of these individuals may favor brown adipogenesis at expense of white adipocyte production.
对肥胖症生理病理学的研究可能会从对瘦人(SP)的研究中获得新的线索。这些人尽管热量摄入很高,远远超过身体需求,但体重增加很少或没有增加。
评估瘦人血清中存在的循环因子如何影响间充质基质细胞(MSC)的脂肪生成。
我们从体重指数(BMI)和热量消耗均正常的健康供体的骨髓中分离出MSC。用从瘦人或正常人(NP)收集的血清预处理MSC培养物。然后进行生物分子测定,以评估对增殖、凋亡、衰老、细胞定向和分化的影响。
瘦人血清预处理影响脂肪细胞的定向,并减少自发脂肪生成。此外,对外源性诱导的脂肪细胞分化的深入分析表明,与正常人血清预处理的样本相比,瘦人血清预处理的样本在分化方面存在显著差异。在瘦人培养的脂肪细胞中,我们观察到脂滴尺寸减小,脂肪甘油三酯脂肪酶表达增加,同时线粒体含量高,在饥饿条件下产生ATP的能力增强。这些数据以及解偶联蛋白1(UCP1)的表达表明,瘦人血清预处理导致偏向棕色脂肪细胞分化。
我们的数据表明,瘦人血清可能促进棕色脂肪生成,而不是白色脂肪细胞分化。这一发现可以解释为什么瘦人尽管热量摄入过多,但身体组成仍正常。我们推测,这些个体血液中存在的一些循环成分可能有利于棕色脂肪生成,而不利于白色脂肪细胞生成。