肿瘤坏死因子-α在脂肪组织中的作用

作为一种由脂肪细胞产生和分泌的多功能细胞因子,肿瘤胚死因子-α(TNF-α)除了在免疫系统中发挥作用外,其在脂肪组织中也具有重要的调控作用,如促进脂肪分解、抑制脂肪合成、抑制脂肪细胞分化、诱导脂肪细胞凋亡等。综合起来看,TNF-α可抑制动物的脂肪沉积。     

肿瘤坏死因子-а在脂肪组织中的作用

作为一种由脂肪细胞产生和分泌的多功能细胞因子,肿瘤胚死因子-а(TNF-а)除了在免疫系统中发挥作用外,其在脂肪组织中也具有重要的调控作用,如促进脂肪分解、抑制脂肪合成、抑制脂肪细胞分化、诱导脂肪细胞凋亡等.综合起来看,TNF-а可抑制动物的脂肪沉积.     

营养素、生长因子与激素对脂肪细胞生长发育影响的研究

哺乳动物体内有白色与褐色两类脂肪组织。现代研究认为,白色脂肪组织除作为体内能量储存器官外,更多承担能够分泌多类激素与因子的内分泌器官角色。对于构成脂肪组织的脂肪细胞而言,其生长发育与多种生理生化及疾病过程的联系密切。脂肪细胞发育分为前期增殖分化与后期发育两个阶段。一般认为,前期脂肪细胞是通过胚胎干细胞—间充质干细胞—脂肪母细胞—前体脂肪细胞—不成熟脂肪细胞—成熟脂肪细胞的途径不断分化而来的,在不同阶段由不同因子诱导细胞逐步向脂肪细胞分化;而后期脂肪细胞发育则是一个受多因素共同作用的过程,这些因素通过不同途径影响细胞发育。目前发现,葡萄糖、维生素、白细胞介素、前体脂肪细胞分化因子、胰岛素等均可通过不同途径在脂肪细胞发育中发挥效用。笔者通过梳理近年相关文献,总结了脂肪细胞类型与来源,以及营养素、生长因子与激素对脂肪细胞发育的影响。随着对影响脂肪细胞发育因素研究的深入,为后续调控肉品品质、治疗营养代谢病或影响其他生理生化进程提供了有力依据。     

猪脂肪细胞生长发育的分子机制及调控因素

脂肪细胞是组成脂肪组织的主要细胞,近年来,脂肪细胞在商品猪生产中备受关注.无论是消费者还是生产者都希望在降低体脂含量提高瘦肉率的同时又不影响肌间脂肪的含量,不影响猪肉的风味品质,这就要求在不同部位对猪脂肪细胞的调控也不相同.猪脂肪细胞的生长发育以及凋亡是一系列脂肪细胞特异基因的表达过程,本文就猪脂肪细胞的生长发育过程及其影响因素等方面做以综述.     

猪脂肪细胞分化的调控

动物体内脂肪的沉积过程一方面是脂肪组织细胞内脂肪的不断合成、蓄积过程,另一方面是脂肪组织脂肪细胞的不断分化过程。因此,脂肪细胞分化的调控在脂肪沉积的调控中占有重要地位。本文阐述了猪脂肪细胞分化的几种调控措施,包括激素调控、生长因子调控、细胞外基质调控、不饱和脂肪酸调控和分化转录因子调控。     

猪脂肪细胞分化的调控

动物体内脂肪的沉积过程一方面是脂肪组织细胞内脂肪的不断合成、蓄积过程。另一方面是脂肪组织脂肪细胞的不断分化过程。因此，脂肪细胞分化的调控在脂肪沉积的调控中占有重要地位。本文阐述了猪脂肪细胞分化的几种调控措施。包括激素调控、生长因子调控、细胞外基质调控、不饱和脂肪酸调控和分化转录因子调控。     

生长因子对猪脂肪细胞分化的调控

动物体脂肪的过度沉积不仅降低畜产品质量,而且还威胁人类健康,已成为动物生产领域亟待解决的问题。近年来的大量研究结果表明,脂肪细胞不仅在调节体内能量平衡中起重要作用,而且在其他各种生理过程,如在脂肪组织的生长和脂肪沉积的自我调节过程中发挥重要作用。动物体内脂肪的沉积过程一方面是脂肪组织细胞内脂肪的不断合成、蓄积过程,另一方面是脂肪组织、脂肪细胞的不断分化过程。而脂肪细胞分化的调控在脂肪沉积的调控中占有重要地位。脂肪组织的发育不同于其他组织,脂肪细胞并不是在胚胎形成的初期阶段就有,而是在胚胎发育后期接近出生…     

DNA甲基化与去甲基化调控脂肪沉积的研究进展

脂肪沉积是一个复杂的生物学过程,受遗传和表观遗传的调控作用。DNA甲基化和去甲基化是表观遗传修饰的重要方式,可通过与转录因子的相互作用或改变染色质的结构调控基因的表达,进而参与机体生长发育和细胞分化等重要的生命过程。动物脂肪沉积是脂肪细胞增殖分化和肥大的结果,脂肪细胞分化是由多能干细胞经前体脂肪细胞向成熟脂肪细胞转化的过程。相关研究表明,转录因子过氧化物酶体增殖物激活受体γ(peroxi-some proliferator activiated receptorγ,PPARγ)和CCAAT增强子结合蛋白家族(CCAAT enchancer binding proteinfamily,CEBPs)在脂肪沉积过程中起关键调控作用。近期研究发现,DNA甲基化可以通过调控脂肪形成过程中相关基因的表达而参与脂肪细胞的分化和脂肪组织的生长发育。去甲基化也可影响动物脂肪沉积过程,但其具体机制目前尚不清楚。作者主要介绍了DNA甲基化和去甲基化的定义、发生位点、生物学功能、参与DNA甲基化和去甲基化过程中的酶及其作用机制,概述了脂肪沉积过程及PPARγ、C/EBPα等转录因子在脂肪沉积过程中的调控作用,重点阐述了DNA甲基化和去甲基化对脂肪形成相关基因的表达和对脂肪细胞分化的影响,旨在为阐明脂肪沉积机制及改善动物肉质品质提供参考。     

DNA甲基化与去甲基化调控脂肪沉积的研究进展

脂肪沉积是一个复杂的生物学过程,受遗传和表观遗传的调控作用。DNA甲基化和去甲基化是表观遗传修饰的重要方式,可通过与转录因子的相互作用或改变染色质的结构调控基因的表达,进而参与机体生长发育和细胞分化等重要的生命过程。动物脂肪沉积是脂肪细胞增殖分化和肥大的结果,脂肪细胞分化是由多能干细胞经前体脂肪细胞向成熟脂肪细胞转化的过程。相关研究表明,转录因子过氧化物酶体增殖物激活受体γ(peroxi-some proliferator activiated receptorγ,PPARγ)和CCAAT增强子结合蛋白家族(CCAAT enchancer binding proteinfamily,CEBPs)在脂肪沉积过程中起关键调控作用。近期研究发现,DNA甲基化可以通过调控脂肪形成过程中相关基因的表达而参与脂肪细胞的分化和脂肪组织的生长发育。去甲基化也可影响动物脂肪沉积过程,但其具体机制目前尚不清楚。作者主要介绍了DNA甲基化和去甲基化的定义、发生位点、生物学功能、参与DNA甲基化和去甲基化过程中的酶及其作用机制,概述了脂肪沉积过程及PPARγ、C/EBPα等转录因子在脂肪沉积过程中的调控作用,重点阐述了DNA甲基化和去甲基化对脂肪形成相关基因的表达和对脂肪细胞分化的影响,旨在为阐明脂肪沉积机制及改善动物肉质品质提供参考。     

抗脂肪细胞特异膜蛋白单克隆抗体对猪皮下脂肪沉积的抑制作用

动物体内脂肪的沉积过程是脂肪细胞不断分化和细胞内脂肪不断合成、蓄积的过程。幼龄动物脂肪组织的增加主要是脂肪细胞的分化，成年动物脂肪组织的增加以脂肪细胞蓄积脂肪为主，仍具有一定细胞分化能力。脂肪细胞在分化过程中除形态学发生变化外，细胞内也发生一系列复杂的生物化学变化，主要表现在分化的早、中和晚期阶段，     

Adipose tissue angiogenesis

A review of adipose tissue angiogenesis includes the morphological and cytochemical development of adipose tissue vasculature and the concept of primitive fat organs. Spatial and temporal relationships between fetal vascular and fat cell development are discussed, including depot- and genetic-dependent arteriolar differentiation. The relationship between connective tissue deposition and elaboration of adipose tissue vasculature is discussed with respect to regulating adipocyte development in a depot-dependent manner. In vitro studies indicated that depot-dependent vascular traits may be attributable to intrinsic growth characteristics of adipose tissue endothelial cells. These studies indicate that adipogenesis may be regulated by factors that drive angiogenesis. Fundamental aspects of angiogenesis, including basement membrane breakdown, vasculogenesis, angiogenic remodeling, vessel stabilization, and vascular permeability were reviewed. Critical angiogenic factors include vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins (Ang), ephrins, matrix metalloproteinases, and the plasminogen enzymatic system. Vascular endothelial growth factor is the most critical factor because it initiates the formation of immature vessels and disruption of a single VEGF allele leads to embryonic lethality in mice. Expression of VEGF is influenced by hypoxia, insulin, growth factors, and several cytokines. Angiogenic factors secreted and/or produced by adipocytes or preadipocytes are discussed. Vascular endothelial growth factor expression and secretion by adipocytes is regulated by insulin and hypoxia, and is associated with adipose tissue accretion. Vascular endothelial growth factor accounts for most of the angiogenic activity of adipose tissue. The proposed role of leptin as an adipogenic factor is reviewed with respect to efficacy on various aspects of angiogenesis relative to other angiogenic factors. The VEGF and leptin genes are both hypoxia inducible, but potential links between VEGF and leptin gene expression have not been examined. Finally, several studies including a study of mice treated with antiangiogenic factors indicate that adipose tissue accretion can be controlled through the vasculature per se.     

Pathology of congenital generalized lipodystrophy in Agpat2-/- mice

Congenital generalized lipodystrophy (CGL) comprises a heterogeneous group of rare diseases associated with partial or total loss of adipose tissue. Of these, autosomal recessive Berardinelli-Seip congenital lipodystrophy (BSCL) is characterized by the absence of metabolically active subcutaneous and visceral adipose tissues. Metabolic abnormalities associated with lipodystrophy include insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes. One form of BSCL has been linked to genetic mutations affecting the lipid biosynthetic enzyme 1-acyl-sn-glycerol 3-phosphate O-acyltransferase 2 (AGPAT2), which is highly expressed in adipose tissue. Precisely how AGPAT2 deficiency causes lipodystrophy remains unresolved, but possible mechanisms include impaired lipogenesis (triglyceride synthesis and storage), blocked adipogenesis (differentiation of preadipocytes to adipocytes), or apoptosis/necrosis of adipocytes. Agpat2(-/-) mice share important pathophysiologic features of CGL previously reported in humans. However, the small white adipose tissue (WAT) depots consisting largely of amoeboid adipocytes with microvesiculated basophilic cytoplasm showed that adipogenesis with deficient lipogenesis was present in all usual locations. Although well-defined lobules of brown adipose tissue (BAT) were present, massive necrosis resulted in early ablation of BAT. Although necrotic or apoptotic adipocytes were not detected in WAT of 10-day-old Agpat2(-/-), the absence of adipocytes in aged mice indicates that these cells must undergo necrosis/apoptosis at some point. Another significant finding in aged lipodystrophic mice was massive pancreatic islet hypertrophy in the face of chronic hyperglycemia, which suggests that glucotoxicity is insufficient by itself to cause β-cell loss and that adipocyte-derived factors help regulate total β-cell mass.     

影响棕色脂肪组织产热活性因素的研究进展

全球性肥胖流行问题愈发严峻,而脂肪组织本身可能是解决这个问题的关键。人和哺乳动物体内存在两种脂肪组织,发挥着截然相反的作用。与白色脂肪组织存储机体过剩的能量不同,棕色脂肪组织中存在独特的解偶联蛋白,能将脂肪酸氧化磷酸化,释放热能,增加能量消耗。因此,通过激活棕色脂肪组织产热,加速体内储存的脂质氧化磷酸化,成为了一种新的预防和治疗肥胖的手段。论文阐述影响棕色脂肪产热活性的因素以及相关机制,旨在为肥胖的治疗提供新的思路和方向。     

Patterns of gene expression in pig adipose tissue: insulin-like growth factor system proteins, neuropeptide Y (NPY), NPY receptors, neurotrophic factors and other secreted factors

Although cDNA microarray studies have examined gene expression in human and rodent adipose tissue, only one microarray study of adipose tissue from growing pigs has been reported. Total RNA was collected at slaughter from outer subcutaneous adipose tissue (OSQ) and middle subcutaneous adipose tissue (MSQ) from gilts at 90, 150, and 210 d (n=5 age(-1)). Dye labeled cDNA probes were hybridized to custom porcine microarrays (70-mer oligonucleotides). Gene expression of insulin-like growth factor binding proteins (IGFBPs), hormones, growth factors, neuropeptide Y (NPY) receptors (NPYRs) and other receptors in OSQ and MSQ changed little with age in growing pigs. Distinct patterns of relative gene expression were evident within NPYR and IGFBP family members in adipose tissue from growing pigs. Relative gene expression levels of NPY2R, NPY4R and angiopoietin 2 (ANG-2) distinguished OSQ and MSQ depots in growing pigs. We demonstrated, for the first time, the expression of IGFBP-7, IGFBP-5, NPY1R, NPY2R, NPY, connective tissue growth factor (CTGF), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) genes in pig adipose tissue with microarray and RT-PCR assays. Furthermore, adipose tissue CTGF gene expression was upregulated while NPY and NPY2R gene expression were significantly down regulated by age. These studies demonstrate that expression of neuropeptides and neurotrophic factors in pig adipose tissue may be involved in regulation of leptin secretion. Many other regulatory factors were not influenced by age in growing pigs but may be influenced by location or depot.     

解偶联蛋白与动物的冷适应

动物的脂肪组织为棕色脂肪组织(brow n ad ipose tissue,BAT)和白色脂肪组织(w h ite ad ipose tissue,W AT)。棕色脂肪组织中含有大量线粒体,是哺乳动物非颤抖产热的主要器官,对动物的体温控制和能量平衡调节起重要作用,位于线粒体内膜的解偶联蛋白(uncoup ling prote in,UCP)的含量和活性是决定其功能的关键因素。作者综述了UCP的结构、UCP基因的多态性及其与肥胖的关系、影响UCPmRNA表达的因素,并对UCP进行了讨论与展望。     

Adipose tissue lipolytic rate in genetically obese and lean swine

In vitro lipolytic rate was determined in adipose tissue from genetically obese and lean pigs. There were about 20 pigs/genetic strain at 25 and 80 kg and 10 pigs/strain at 50 kg body weight. When expressed on a cellular basis, the in vitro adipose tissue basal (no exogenous hormone) lipolytic rate was similar in obese and lean pigs at 25 and 50 kg body weight. At 80 kg body weight the basal rate was greater in obese than in lean pigs. The in vitro adipose tissue epinephrine-stimulated lipolytic rate expressed on a cell basis was greater at 25 kg, was similar at 50 kg body weight and tended (P less than or equal to .1) to be greater at 80 kg in obese compared with lean pigs. The in vitro sensitivity of lipolysis to epinephrine was slightly greater in lean compared with obese pigs. The data obtained in vitro indicate that obese pigs do not have low adipose tissue lipolytic rates compared with lean pigs. Consequently, adipose tissue lipolysis does not appear to be a major metabolic factor leading to the excessive fat accretion in these obese pigs.