筋膜前脂肪细胞的特征与定位研究

Adult adipose precursor cells are thought to originate from stromal vascular cells, pericytes, and endothelial cells of blood vessels within adipose tissue, and also bone marrow cells resident in non-adipose tissue, although the last two types of adipocyte progenitors remain under debate. Fascia consists of particularly abundant collagen and elastic fibers and fibrocytes, and a few adipocytes and various migrating white blood cells and constitutes a continuous, elastic sheet of connective tissues that extends throughout the body. Fasciae form ubiquitous frameworks to penetrate and separate adipose tissue, and adipose tissue may form and localize between layers of fasciae. Our preliminary observations show that the fragment of fascial tissue and cells isolated from fascia are capable of spontaneous differentiation into adipocytes in culture in the absence of adipogenic inducers, and are more efficiently differentiated into adipocytes upon induction of adipogenesis. In this project, we select the fasciae of rat limbs as experimental samples, because the fascia in rat, different from the fascia in human, contains a less amount of mature adipocytes and is easily dissected from adjacent tissues. We aim to investigate the characteristics of the fascial preadipocytes by using stem cell surface markers and flow cytometry analysis, and identify localization and distribution of these adipocyte progenitors in situ in fasciae. We investigate the regulation of adipocyte differentiation of fascial progenitors in different physiological conditions, such as gender, age, fasting, and excessive nutrients. We also investigate whether adipocyte differentiation of fascial progenitors participates in the pathgenesis of high fat diet induced obesity. Fascia could be another origin of adipose tissue and adipocyte progenitors. We expect that this study could be able to uncover the veil on this novel type of preadipocytes resident in fascia.

脂肪前体细胞可能源自脂肪组织中的血管基质细胞、周细胞、内皮细胞，以及非脂肪组织来源的骨髓造血干细胞，但后二者存在很大争议。筋膜是连续分布的结缔组织，由大量胶原和弹性纤维组成，含有较多的纤维细胞和少量巨噬细胞、肥大细胞和脂肪细胞。筋膜和脂肪均起源于中胚层。人体内筋膜无处不在，可延伸于脂肪组织中；而脂肪分布广泛，能填充于筋膜层之间。与人的筋膜不同，大鼠肌肉筋膜几乎不含脂肪细胞，容易分离且不污染其它组织如脂肪。我们发现，离体培养的大鼠筋膜组织块和筋膜细胞能自发或诱导分化为脂肪细胞，分化效率很高。筋膜存在大量的脂肪前体细胞，提示筋膜可能是脂肪细胞的发源地。本课题拟研究，筋膜的脂肪前体细胞亚群的干细胞标志物特征；其在筋膜组织上的定位和分布特征；筋膜前脂肪细胞在不同的营养条件下如何分化，是否参与高脂饮食诱导的肥胖。我们期望这一研究能揭开筋膜前脂肪细胞的面纱，发现筋膜是脂肪细胞的另一来源。

本课题采用不含或少含脂肪细胞、容易分离、且不粘连其它组织的大鼠骨骼肌筋膜为实验材料，研究筋膜前脂肪细胞的干细胞标志物特征、在体组织定位和分布特征；研究其分化的脂肪细胞抵抗激素刺激脂肪分解的机制；研究各种生理和病理条件下，筋膜前脂肪细胞的分化规律。通过本课题研究我们提出两个新的关于脂肪的组织细胞学观点：一、提出浅筋膜是脂肪组织发源地的新观点：筋膜是脂肪组织的一个发源地。浅筋膜连续分布于皮肤下和骨骼肌之间。大鼠浅筋膜含大量前脂肪细胞，能高效自发地或经诱导分化为脂肪细胞。出生后，筋膜脂肪前体细胞陆续分化为脂肪细胞，沿血管形成二维单层脂肪细胞薄层，随后新生的微血管沿着脂肪细胞薄层向外、向前延伸，并不断向上向外堆积生长，最终形成三维的脂肪组织。此后，原有筋膜依其固有的组织学特性，将自发延伸进入刚形成的三维新生脂肪中，成为新生脂肪的内部筋膜，并在脂肪组织内继续提供脂肪前体细胞，以保证新生脂肪组织的自我扩增。这一脂肪起源于筋膜的模型，既能解释脂肪组织的新生，也能解释已有脂肪的扩增，与人体浅筋膜和皮下脂肪犬牙交错分布的解剖学现象是一致的。二、提出筋膜脂肪细胞是一种新的脂肪细胞类型：我们研究了筋膜脂肪干细胞和筋膜脂肪细胞的形态学特征以及生理生化反应和代谢特征，发现与附睾、腹股沟脂肪细胞相比，筋膜脂肪细胞的脂滴较小较碎，大小离散，少串珠状结构，显示明显的形态异质性。筋膜脂肪细胞的基础脂肪分解率增加，因地表达β3和β1肾上腺素受体而抵抗儿茶酚胺刺激的脂肪分解反应，但beta肾上腺素受体后cAMP/PKA途径的脂肪分解通路正常。目前白色脂肪细胞可以分为两个代谢类型类型：内脏白色脂肪细胞，皮下白色脂肪细胞。与这两种类型的白色脂肪细胞相比，筋膜脂肪细胞来源于不同的前体干细胞，具有不同的细胞形态，具有不同的脂肪分解代谢特征。据此我们提出，筋膜脂肪是一种新的白色脂肪细胞，不同与常见的内脏、皮下部位的白色脂肪细胞。