肝X 受体在脂肪生成和脂肪细胞形成中的作用

肝X 受体（LXRs）是核受体超家族成员,其通过激活固醇调节元件结合蛋白-1c,促进脂肪的从头合成。此外,LXRs与脂肪细胞的形成亦有密切联系。LXRs的激活可能参与了前脂肪细胞向脂肪细胞分化。介绍肝X受体在脂肪生成和脂肪细胞形成过程中所起的作用及其分子机制,旨在为胚胎干细胞向脂肪细胞定向诱导分化以及多囊卵巢综合征等肥胖相关疾病的发病机制研究提供方向。     

LXRs与疾病

肝X受体（LXRs）是核受体超家族的成员，包括两种亚型LXRa（NR1H3）和LXRβ（NR1H2）。LXRs被配体激活后，与类固醇X受体（R）（Rs）形成异源二聚体，再与其靶基因的LXR调控元件结合，通过调节靶基因的转录，调控机体的代谢和炎症反应。     

020 LXRs 与疾病

肝X受体(LXRs)是核受体超家族的成员,包括两种亚型LXRα(NR1H3)和LXRβ(NR1H2).LXRs被配体激活后,与类固醇X受体(RXRs)形成异源二聚体,再与其靶基因的LXR调控元件结合,通过调节靶基因的转录,调控机体的代谢和炎症反应.     

PPARγ与多囊卵巢综合征胰岛素抵抗的研究

PPAR即过氧化物酶体增殖体激活受体 ,是核受体超家族成员之一。PPARγ主要表达于脂肪组织 ,它可以促进脂肪细胞分化、调控多种脂肪细胞分泌的蛋白质因子基因的表达。近年发现PPARγ基因的多态性及对脂肪细胞因子的调控作用与PCOSIR的发生密切相关 ;而噻唑烷二酮类药物激活PPARγ后可以改善PCOSIR的研究结果 ,进一步说明PPARγ的作用可能是PCOSIR多种形成机制中的重要途径之一。     

PPARγ与多囊卵巢综合征胰岛素抵抗的研究

PPAR即过氧化物酶体增殖体激活受体，是核受体超家族成员之一。PPARγ主要表达于脂肪组织，它可以促进脂肪细胞分化、调控多种脂肪细胞分泌的蛋白质因子基因的表达。近年发现PPARγ基因的多态性及对脂肪细胞因子的调控作用与PCOS IR的发生密切相关；而噻唑烷二酮类药物激活PPARγ后可以改善PCOS IR的研究结果，进一步说明PPARγ的作用可能是PCOS IR多种形成机制中的重要途径之一。     

小鼠胚胎干细胞向脂肪细胞分化的分子机制

随着肥胖患者不断增多,通过研究小鼠胚胎干细胞向脂肪细胞分化的分子机制,探讨肥胖发生机制已成为研究热点。研究认为,过氧化物酶体增殖物激活受体(PPARγ)、CCAAT增强子结合蛋白(C/EBPα)及脂肪细胞决定和分化依赖因子1和类固醇调控元件结合蛋白(ADD1/SREBP-1c)为前脂肪细胞系向脂肪细胞分化的关键转录因子,其他的调节因子如糖皮质激素(GC)、丝裂原活化蛋白激酶P38(P38MAPK)、生长激素(GH)等大多通过这些关键转录因子发挥诱导或抑制作用。     

小鼠胚胎干细胞向脂肪细胞分化的分子机制

随着肥胖患者不断增多,通过研究小鼠胚胎干细胞向脂肪细胞分化的分子机制,探讨肥胖发生机制已成为研究热点.研究认为,过氧化物酶体增殖物激活受体(PPARγ)、CCAAT增强子结合蛋白(C/EBPα)及脂肪细胞决定和分化依赖因子1和类固醇调控元件结合蛋白(ADD1/SREBP-1c)为前脂肪细胞系向脂肪细胞分化的关键转录因子,其他的调节因子如糖皮质激素(GC)、丝裂原活化蛋白激酶P38(P38MAPK)、生长激素(GH)等大多通过这些关键转录因子发挥诱导或抑制作用.     

肝X受体与急性肺损伤研究进展

肝X受体(liver X receptors,LXRs)是孤核受体家族的重要成员,由Willy等[1]人最初从肝cD-NA文库中分离而得,因在肝脏表达丰富而命名.LXRs调节胆固醇的输出、胆汁酸的生成及脂质转运蛋白的合成,从而调控脂质的动态平衡.近年来发现,LXRs还能抑制巨噬细胞和其他炎症细胞的炎症因子和炎症介质的释放,从而在一定的程度上减轻炎症反应.最新研究表明,LXRs在肺泡巨噬细胞、肺泡上皮细胞以及肺组织中有一定的表达,在肺组织的LXRs能通过各种途径减轻急性肺损伤.笔者就LXRs的结构、分型和分布,LXRs的配体及转录调节模式,以及LXRs的抗炎作用和对急性肺损伤的保护作用作一综述.     

脂肪细胞分化过程中脂联素受体的时序性表达(英文)

目的探讨SW872前脂肪细胞分化过程中脂联素受体基因表达的时序性变化。方法体外培养,0.6mM油酸诱导SW872前脂肪细胞分化24h,48h,72h,油红0染色观察细胞内脂肪的聚积;RT-PCR方法检测不同分化时间点脂联素受体1及脂联素受体2 mRNA水平。结果0.6mM油酸诱导分化72h,能成功地将SW872前脂肪细胞分化为成熟的脂肪细胞。SW872前脂肪细胞表达两种脂联素受体,诱导分化刺激24h,脂联素受体1 mRNA水平是诱导分化前的1.95倍,脂联素受体2 mRNA水平是诱导分化前的1.61倍;诱导分化刺激48h,脂联素受体1 mRNA水平是诱导分化前的2.16倍,脂联素受体2 mRNA水平是诱导分化前的2.34倍;诱导分化72h,脂联素受体1 mRNA水平是诱导分化前的2.54倍,脂联素受体2 mRNA水平是诱导分化前的4.09倍。结论SW872脂肪细胞表达脂联素两种受体增殖,且两种脂联素受体的基因表达呈分化相关性。     

鱼油帮助燃烧脂肪

<正>最近一项研究发现,鱼油能够将储存脂肪的细胞变为燃烧脂肪的细胞,这可能有助于抑制中年人的体重增长。研究人员解释说,鱼油能够激活消化道内的受体,激活交感神经系统,进而诱导脂肪细胞进行脂肪的代谢。脂肪组织并非全部都用来储存脂肪。白色脂肪细胞能够储存脂肪帮助维持能量供应,而棕色脂肪细胞主要负责代谢脂肪以维持正常体温。棕色脂肪细胞在婴儿体内比较丰富,但随着年龄增长逐渐减少,成年以后大部分棕色脂     

Adenovirus-36 as one of the causes of obesity: the review of the pathophysiology

The dramatic increase of people affected by obesity worldwide seems to be influenced by external factors independent of eating habits, physical exercise, or genetic characteristics. There may be a number of such factors, but one hypothesis is that there is person-to-person transmission, causing an epidemic effect, as occurs with infectious diseases. In animal models, experimental infection with human adenovirus-36 (Adv36) causes obesity. Humans cannot be experimentally infected, but a number of studies found a correlation of positive serology for Adv36 with overweight/obesity in humans. In vitro studies have shown that Adv36 accelerates the differentiation and proliferation of preadipocytes into adipocytes and increases their lipid concentration. Another viral mechanism involved is the activation of a noninsulin-dependent process that increases glucose uptake, mainly in adipose tissue and muscle. The increased glucose, coupled with increased lipogenesis due to increased fatty acid synthase and the action of peroxisome proliferator-activated receptor gamma (PPAR-gamma) in stimulating adipocyte differentiation from adult stem cells enhances fat accumulation within the adipocytes. In studies conducted to date, the Adv36 E4 open reading frame 1 gene (E4orf1), which activates the glucose transporter protein isoform 4 (GLUT4) and glucose transporter protein isoform 1 (GLUT1) glucose transporters, appears to play a major role in the virus adipogenesis. The aim of this study was to review the pathophysiology of obesity and the role of Adv36.     

Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism

Background: Bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE), used in manufacturing coatings and resins, leach from packaging materials into food. Numerous studies suggested that BPA and BADGE may have adverse effects on human health, including the possibility that exposure to such chemicals can be superimposed on traditional risk factors to initiate or exacerbate the development of obesity. BPA is a suspected obesogen, whereas BADGE, described as a peroxisome proliferator–activated receptor gamma (PPARγ) antagonist, could reduce weight gain.Objectives: We sought to test the adipogenic effects of BADGE in a biologically relevant cell culture model.Methods: We used multipotent mesenchymal stromal stem cells (MSCs) to study the adipogenic capacity of BADGE and BPA and evaluated their effects on adipogenesis, osteogenesis, gene expression, and nuclear receptor activation.Discussion: BADGE induced adipogenesis in human and mouse MSCs, as well as in mouse 3T3-L1 preadipocytes. In contrast, BPA failed to promote adipogenesis in MSCs, but induced adipogenesis in 3T3-L1 cells. BADGE exposure elicited an adipogenic gene expression profile, and its ability to induce adipogenesis and the expression of adipogenic genes was not blocked by known PPARγ antagonists. Neither BADGE nor BPA activated or antagonized retinoid “X” receptor (RXR) or PPARγ in transient transfection assays.Conclusions: BADGE can induce adipogenic differentiation in both MSCs and in preadipocytes at low nanomolar concentrations comparable to those that have been observed in limited human biomonitoring. BADGE probably acts through a mechanism that is downstream of, or parallel to, PPARγ.     

Activation of LXRs Reduces Oxysterol Lipotoxicity in RPE Cells by Promoting Mitochondrial Function

Effective treatments for age-related macular degeneration (AMD), the most prevalent neurodegenerative form of blindness in older adults, are lacking. Genome-wide association studies have identified lipid metabolism and inflammation as AMD-associated pathogenic changes. Liver X receptors (LXRs) play a critical role in intracellular homeostases, such as lipid metabolism, glucose homeostasis, inflammation, and mitochondrial function. However, its specific role in AMD and its underlying molecular mechanisms remain unknown. In this study, we investigated the effects of lipotoxicity in human retinal pigmental epithelial (ARPE-19) cells and evaluated how LXRs reduce 7-ketocholesterol (7KCh) lipotoxicity in RPE cells using models, both in vivo and in vitro. A decrease in oxidative lipid accumulation was observed in mouse retinas following the activation of the LXRs; this result was also confirmed in cell experiments. At the same time, LXRs activation reduced RPE cell apoptosis induced by oxysterols. We found that oxysterols decreased the mitochondrial membrane potential in ARPE-19 cells, while LXR agonists counteracted these effects. In cultured ARPE-19 cells, activating LXRs reduced p62, mTOR, and LC3I/II levels, and the knockdown of LXRs elevated the expression of these proteins, indicating that activating LXRs could boost mitophagy. The findings of this study suggest LXR-active pharmaceuticals as a potential therapeutic target for dry AMD.     

The protective effects of steamed ginger on adipogenesis in 3T3-L1 cells and adiposity in diet-induced obese mice

BACKGROUND/OBJECTIVESThe steamed ginger has been shown to have antioxidative effects and a protective effect against obesity. In the present study, we investigated the effects of ethanolic extract of steamed ginger (SGE) on adipogenesis in 3T3-L1 preadipocytes and diet-induced obesity (DIO) mouse model.MATERIALS/METHODSThe protective effects of SGE on adipogenesis were examined in 3T3-L1 adipocytes by measuring lipid accumulations and genes involved in adipogenesis. Male C57BL/6J mice were fed a normal diet (ND, 10% fat w/w), a high-fat diet (HFD, 60% fat w/w), and HFD supplemented with either 40 mg/kg or 80 mg/kg of SGE for 12 weeks. Serum chemistry was measured, and the expression of genes involved in lipid metabolism was determined in the adipose tissue. Histological analysis and micro-computed tomography were performed to identify lipid accumulations in epididymal fat pads.RESULTSIn 3T3-L1 cells, SGE significantly decreased lipid accumulation, with concomitant decreases in the expression of adipogenesis-related genes. SGE significantly attenuated the increase in body, liver, and epididymal adipose tissue weights by HFD. Serum total cholesterol and triglyceride levels were significantly lower in SGE fed groups compared to HFD. In adipose tissue, SGE significantly decreased adipocyte size than that of HFD and altered adipogenesis-related genes.CONCLUSIONSIn conclusion, steamed ginger exerted anti-obesity effects by regulating genes involved in adipogenesis and lipogenesis in 3T3-L1 cell and epididymal adipose tissue of DIO mice.     

Arctiin inhibits adipogenesis in 3T3-L1 cells and decreases adiposity and body weight in mice fed a high-fat diet

BACKGROUND/OBJECTIVES

The purpose of this study was to examine the effects and associated mechanisms of arctiin, a lignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obese mice fed a high-fat diet on adiposity were examined.

MATERIALS/METHODS

3T3-L1 cells were treated with arctiin (12.5 to 100 µM) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes related to adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were first fed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin (HF + AC) for four weeks.

RESULTS

Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiin treatment significantly decreased the protein levels of the key adipogenic regulators PPARγ and C/EBPα, and also significantly inhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatly increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fat diet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC than in the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue.

CONCLUSIONS

Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of PPARγ and C/EBPα and the activation of AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.