Identification of a Membrane Receptor for Retinol-Binding Protein Functioning in the Cellular Uptake of Retinal

Retinol-binding protein (RBP) is the transport protein that carries retinol in the circulation from the liver to its target tissues. The existence of a cell-surface receptor on the target cells, which mediates the uptake of retinol from RBP, has been known since 1975. Recently, it was identified as an integral transmem-brane protein named STRA6 that is inducible by retinoic acid in certain cancer cells. The receptor was found to be highly specific for RBP, with high affinity, and to be localized in all tissues known to require retinol for their function, particularly the pigment epithelium of the eye.     

大叶紫薇叶中降血糖活性成分的筛选

为筛选大叶紫薇叶中具有降血糖活性的成分,采用3T3-L1细胞葡萄糖消耗模型作为检测手段,对大叶紫薇叶提取物采用HP-20树脂吸附、溶剂萃取、制备薄层分离和制备高效液相分离,导向筛选具有降血糖作用的各分离组分.结果发现,大叶紫薇叶中corosolic acid、熊果酸和总三萜具有降血糖活性.     

Desensitization of the adipocyte A(1) adenosine receptor during untreated experimental diabetes mellitus

We examined the changes that occur in the adenosine receptor system during diabetes mellitus. Experimental diabetes mellitus was induced in male Lewis rats with streptozocin (65 mg/kg), and A₁ adenosine receptor binding was characterized with [¹²⁵I]N ⁶-2-(4-aminophenyl) ethyladenosine. In adipocytes, high-affinity A₁ adenosine receptor binding decreased from 1466±228 of protein to 312±123 fmol/mg of protein (p<0.01) following 14 d of untreated diabetes mellitus. Neither the dissociation constant (K _d=1.3±0.2 nM) nor the basal level of adenylate cyclase activity (2.8±1.1 pmol cAMP/mg of protein/min) was altered by diabetes mellitus. The dose-response curve for the inhibition of adenylate cyclase byN ⁶-R-phenylisopropyladenosine (R-PIA), however, did show a rightward shift, indicating that diabetic adipocyte membranes were less sensitive to the effects of adenosine than nondiabetic adipocyte membranes. In contrast, the A₁ adenosine receptor-binding characteristics and adenylate cyclase dose-response curve for cerebral cortical tissue were unchanged by diabetes. These findings suggest that diabetes has tissue-specific effects on the A₁ adenosine receptor system. Furthermore, the decreased sensitivity to adenosine potentially worsens the hyperlipidemia associated with diabetes mellitus. Such alterations in the adenosine receptor system may play a previously undescribed role in the pathophysiology of diabetes mellitus and may help explain why some organs are severely affected by diabetes, but others are relatively spared. Understanding these alterations in adenosine receptor function may lead tonovel therapies of this common metabolic disease.     

Inherent Abnormalities of Fat Cells from Massively Obese Individuals

In vitro investigations into adipose cell dynamics have revealed intrinsic characteristics of massively obese individuals' cells that could contribute to a relatively intractable expanded fat mass. Morbidly corpulent peoples' preadipocytes replicate to a greater degree than those from lean individuals. Coupled with exaggerated differentiation this enhanced growth would result in a greater number of fat cells which would increase adipose tissue mass. The relative resistance to de-differentiation that adipocytes from the massively obese demonstrate would contribute to stability of an increased number of adipocytes further exacerbating the problem. The increased message of an energy sensing protein, the obese gene product, suggests that the morbidly obese are insensitive to its action. Together these attributes provide a strong argument for a significant genetic role in the pathogenesis of obesity.     

miR-320-3p 调控脂肪细胞分化的研究

目的探讨miR-320-3p 对脂肪细胞分化的影响。方法分离并培养小鼠骨髓间充质干细胞（MSCs）,并对其进行脂肪细胞诱导分化3 d,用qRT-PCR 检测miR-320-3p 在成脂分化过程中的表达水平。在骨髓基质细胞系 ST2 中转染miR-320-3p,对其进行成脂方向诱导分化,用油红O 染色和qRT-PCR 检测miR-320-3p 对ST2 成脂分化的影响。结果MSCs 向脂肪细胞分化过程中miR-320-3p 表达增加（P < 0.01）;与转染阴性对照NC mimics 相比,ST2 细胞转染miR-320-3p mimics 后油红O 染色显示脂肪细胞明显增多,脂肪细胞特异性转录因子过氧化物酶体增殖物激活受体γ(PPARγ)、CCAAT 增强子结合蛋白α（C/EBPα）和脂肪细胞脂肪酸结合蛋白4（FABP4）基因表达显著升高,差异有统计学意义（P < 0.05）。结论miR-320-3p 可促进ST2 向脂肪细胞分化。     

缺氧对成熟脂肪细胞去分化影响的实验研究

目的 研究缺氧环境下成熟脂肪细胞体外培养的形态学变化,探讨缺氧环境对成熟脂肪细胞去分化的影响.方法 从成人吸脂术后抽吸物提取脂肪组织来源的干细胞,诱导为成熟脂肪细胞,在缺血缺氧的环境下培养.观察各时间段细胞的形态变化.结果 由脂肪组织来源的干细胞诱导而成的成熟脂肪细胞,在缺氧环境培养数日后,细胞从圆形变为可持续分裂的成纤维细胞状细胞.结论 成熟的脂肪细胞在一定条件下可以去分化为成纤维细胞状细胞.     

Astragaloside IV attenuates lipolysis and improves insulin resistance induced by TNFalpha in 3T3-L1 adipocytes

Increased circulating free fatty acid (FFA) concentrations have been demonstrated to potentially link obesity, insulin resistance and cardiovascular diseases. Astragaloside IV (AS-IV) is a saponin which is widely used in traditional Chinese medicine to treat type 2 diabetes and cardiovascular diseases. The purpose of the present study was to examine the effects of AS-IV on the lipolysis and insulin resistance induced by tumor necrosis factor-alpha (TNFalpha) in cultured 3T3-L1 adipocytes. TNFalpha promotes lipolysis in mammal adipocytes via the mitogen activated protein kinase (MAPK) family resulting in reduced expression/function of perilipin. Application of AS-IV inhibited TNFalpha-induced accelerated lipolysis in a dose-dependent manner, which was compatible with suppressed phosphorylation of ERK1/2 and reversed the downregulation of perilipin. Moreover, TNFalpha induced downregulation of key enzymes in lipogenesis, including LPL, FAS and GPAT, were also attenuated by AS-IV. Further studies showed that AS-IV improved TNFalpha-induced insulin resistance in 3T3-L1 adipocytes. This study provides the first direct evidence of the antilipolytic action of AS-IV in adipocytes, which may allow this agent to decrease the circulating FFA levels, thus increase insulin sensitivity and treat cardiovascular diseases.     

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 µg/mL, n = 9 vs. 1.4 ± 0.3 µg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity.     

Branched-Chain Fatty Acids Alter the Expression of Genes Responsible for Lipid Synthesis and Inflammation in Human Adipose Cells

Recently, we have demonstrated a decreased level of iso-branched-chain fatty acids (iso-BCFAs) in patients with excessive weight. However, it is still unclear whether BCFAs may influence lipid metabolism and inflammation in lipogenic tissues. To verify this, human visceral adipocytes were cultured with three different concentrations of selected iso-BCFA (14-methylpentadecanoic acid) and anteiso-BCFA (12-methyltetradecanoic acid), and then the expression of genes associated with lipid metabolism (FASN—fatty acid synthase; SREBP1—sterol regulatory element-binding protein 1; SCD1—stearoyl-CoA desaturase; ELOVL4—fatty acid elongase 4; ELOVL6—fatty acid elongase 6; FADS2—fatty acid desaturase 2; FADS1–fatty acid desaturase 1) and inflammation (COX-2—cyclooxygenase 2; ALOX-15—lipoxygenase 15; IL-6—interleukin 6) were determined. This study demonstrates for the first time that incubation with iso-BCFA decreases the expression of adipocyte genes that are associated with lipid metabolism (except FASN) and inflammation. These findings suggest that changes in the iso-BCFA profile in obese patients may contribute to adipose inflammation and dyslipidemia. Further studies should evaluate whether iso-BCFA supplementation in obese patients would be beneficial.     

体外培养的人脂肪间充质干细胞生物学特性的研究

目的:了解体外培养的人脂肪间充质干细胞的生物学特性及其体外成脂和成骨的能力.方法:体外培养人脂肪间充质干细胞并传代计数,行成骨和成脂诱导,流式细胞仪检测其细胞增殖周期与表面分子.结果:人脂肪干细胞经过体外培养均一的阳性表达CD44、CD106,而CD49d、CD34、CD45和HLA-DR表达阴性.细胞周期分析表明:G0/G1、S和G 2/M所占比例分别为79.1%、19.7%和1.3%.分离细胞在诱导体系下可以向成骨和成脂方向分化.结论:脂肪间充质干细胞具有特殊的生物学特点,体外能够向成骨和成脂方向分化.