Adipocyte-derived lipoprotein lipase induces macrophage activation and monocyte adhesion: role of fatty acids

Objective: We evaluated the effect of adipocyte‐derived lipoprotein lipase (LPL) on macrophage activation and monocyte adhesion and the role of fatty acids in these effects. Research Methods and Procedures: 3T3‐L1 adipocytes were incubated with heparin or insulin to induce LPL secretion; then adipocyte conditioned media (CM) were added to cultured J774 macrophages or human aortic endothelial cells (HAECs). Macrophage cytokine production and monocyte adhesion to HAECs were determined. Results: Incubation of macrophages with heparin‐ or insulin‐treated adipocyte CM increased tumor necrosis factor α, interleukin‐6, and nitric oxide production by these cells. LPL neutralization and heparinase treatment prevented these effects. Addition of active LPL or palmitate to cultured macrophages replicated these effects. Blockade of leptin also reduced the effect of insulin‐treated adipocyte CM on macrophage inflammatory changes. Induction of macrophage cytokine secretion by leptin was prevented by LPL immunoneutralization. Finally, addition of CM of heparin‐ or insulin‐treated adipocytes to HAECs stimulated monocyte adhesion to these cells, an effect that was abrogated by an anti‐LPL antibody. This effect was reproduced by treating HAECs with active LPL or palmitate. Discussion: These results point to an effect of LPL‐mediated lipolysis in macrophage activation and monocyte adhesion.     

法尼酯X受体对肝脂酶表达的影响

目的:探讨法尼酯X受体(farnesoid X receptor,FXR)对肝脂酶(hepatic lipase,HL)表达的影响。方法:用FXR激动剂CDCA作用人肝癌细胞株(HepG2),用RT-PCR和Western blotting检测HL的表达情况。结果:用不同浓度的CDCA(25μmol/L、50μmol/L、75μmol/L)分别作用HepG2细胞6h、12h、24h、48h后,HL的mRNA和蛋白质水平呈时间和剂量依赖性下调。结论:FXR激动剂可抑制肝脂酶的表达。     

绵羊肌肉中FAS基因和HSL基因的发育性变化及其对肌内脂肪含量的影响

选取不同日龄的雄性哈萨克羊和新疆细毛羊共54只,屠宰后取背最长肌,用索氏抽提法检测肌内脂肪(intramuscular fat,IMF)含量,用荧光实时定量PCR法检测肌肉脂肪酸合成酶(fatty acid synthase,FAS)和激素敏感脂肪酶(hormone-sensitive lipase,HSL)基因表达的发育性变化,并分析基因表达对肌内脂肪沉积的影响。结果表明:1)随着日龄的增加,雄性哈萨克羊的IMF含量持续上升,各生长时期差异显著(P<0.05),而新疆细毛羊的IMF含量在各生长时期无显著差异(P>0.05)。雄性哈萨克羊的IMF含量30~90日龄期间极显著高于新疆细毛羊(P<0.01)。2)FAS基因mRNA水平在哈萨克羊肌肉中初生时最高(P<0.05),然后随日龄的增加呈下降趋势;在新疆细毛羊肌肉中,FAS mRNA水平表现出"下降-上升-下降-上升"的发育模式,其中60日龄显著高于90日龄(P<0.05),其余日龄之间差异不显著。HSL基因在2品种绵羊肌肉中的表达模式基本类似,在哈萨克羊肌肉中随年龄的增加而下降,初生时的水平显著高于60~90日龄(P<0.05);在新疆细毛羊中30日龄时达到最高(P<0.01),到60日龄时下降到最低(P<0.05),随后保持这种低表达水平。3)FAS和HSL基因mRNA的表达量均与哈萨克羊IMF含量呈负相关,相关系数分别为:r=-0.485(P=0.02),r=-0.423(P=0.05);在哈萨克羊中两基因表达量水平比值(FAS:HSL)与IMF呈极显著负相关r=-0.552(P=0.01)。在新疆细毛羊中两基因的表达水平及比值均与IMF无显著相关性(P>0.05)。     

中国人群脂蛋白脂肪酶基因突变与高脂血症的相关性研究

为进行脂蛋白脂肪酶基因突变与中国人群高脂血症的相关性研究,采用单链构象多态性分析结合DNA序列测定的方法,对386例(其中108例高脂血症患者,278例正常对照)中国人群进行突变筛查。结果发现1个新的沉默突变L103L,1个错义突变P207L,3个剪接突变Int3/3′-ass/C(-6)→T和普遍存在的S447X多态性,其中发生在高脂血症组的P207L杂合子为亚洲首报,并对先证者的家系进行了研究,认为P207L是家族性高脂血症的病因之一,而在正常对照组中也有发现的Int3/3′-ass/C(-6)→T,对以往研究认为其是高脂血症易患因素的观点提出了相反的报告,对于普遍认为有益的多态性位点S447X,进一步研究认为其对于正常人群,特别是健康男性的保护作用更强。结论:脂蛋白脂肪酶基因变异与高脂血症的相关性十分复杂多样,大规模的人群筛查具有重要意义。     

固定化脂肪酶性质及其应用研究

利用以四甲氧基硅烷(TMOS)和甲基三甲氧基硅烷(MTMS)为前驱体的溶胶-凝胶法(sol-gel)固定洋葱假单胞菌属脂肪酶,考查了固定化酶和游离酶的酶学性质及催化不同油脂酯交换合成生物柴油的情况。结果表明,80℃以下固定化酶能保持80%以上的酶活,而游离酶在50℃以后活力急剧下降,到80℃残余酶活约为10%;固定化酶在体积分数50%的甲醇中处理48 h能保持85%的酶活,在体积分数90%的乙醇中处理48h能保持31%的酶活,而游离酶残余酶活只有69%和0;在酯交换反应中固定化酶的催化效率比游离酶高10%~20%,且固定化酶重复使用11次后仍能保持60%的酶活。结果显示,酶经过固定化后稳定性和催化活性显著提高。     

阿霉素注射剂量对肾病综合征大鼠脂蛋白脂酶和卵磷脂胆固醇酰基转移酶水平的影响

摘要 目的：探讨阿霉素注射剂量对肾病综合征（nehpmtic syndrome,NS）大鼠脂蛋白脂酶和卵磷脂胆固醇酰基转移酶（Leci-thin cholesterol acyltransferase,LCAT）水平的影响。方法：64只SD大鼠随机平分为四组-对照组、小剂量阿霉素组、中剂量阿霉素组与高剂量阿霉素组,四组大鼠经尾静脉一次性注射阿霉素0 mg/kg、2 mg/kg、4 mg/kg、8 mg/kg,检测造模后不同时间点大鼠肾脏脂蛋白脂酶和卵磷脂胆固醇酰基转移酶水平变化情况。结果：小剂量阿霉素组、中剂量阿霉素组与高剂量阿霉素组造模后7 d、14 d、21 d的体重与每日采食量、血肌酐与尿素氮都低于对照组（P<0.05）,24 h尿蛋白高于对照组（P<0.05）,且存在剂量依赖性,三组间对比差异有统计学意义（P<0.05）。小剂量阿霉素组、中剂量阿霉素组与高剂量阿霉素组造模后21 d、28 d的肾脏脂蛋白脂酶和卵磷脂胆固醇酰基转移酶相对表达水平低于对照组（P<0.05）,且存在剂量依赖性,三组间对比差异有统计学意义（P<0.05）。结论：小剂量阿霉素可抑制大鼠肾脏脂蛋白脂酶和卵磷脂胆固醇酰基转移酶的表达,能快速有效建立肾病综合征大鼠模型,具有很好的模拟造模效果。     

脂蛋白脂肪酶基因敲除对急性高脂血症性胰腺炎所致肺损伤的影响及其机制研究

摘要 目的：研究脂蛋白脂肪酶（lipoprotein lipase,LPL）基因敲除对雨蛙素诱导的高脂血症急性胰腺炎小鼠肺损伤的影响。方法：将C57BL/6小鼠分为三组,Control组和AP-Model组为野生型C57 BL/6小鼠,LPL ko组为LPL基因敲除C57 BL/6小鼠;Control组小鼠正常饲养,AP-Model和LPL ko组小鼠建立高脂血症性急性胰腺炎模型,比较三组小鼠死亡率、胰腺和肺病理损伤以及血清淀粉酶（amylase, AMY）、丙二醛（malondialdehyde, MDA）、肿瘤坏死因子-α（Tumor necrosis factor-α, TNF-α）和白介素-6（Interleukin-6, IL-6）含量。结果：急性胰腺炎建立48 h后,Control组、AP-Model组和LPL ko组小鼠死亡率分别为0 %、20 %和40 %。与Control组相比,AP-Model组和LPL ko组小鼠急性胰腺炎诱导24和48 h后的胰腺和肺组织湿/干重比值,胰腺和肺组织病理评分,血清AMY、MDA、TNF-α和IL-6含量均显著升高（P<0.05）;与AP-Model组相比,LPL ko组小鼠急性胰腺炎诱导24和48 h后的胰腺和肺组织湿/干重比值,胰腺和肺组织病理评分,血清AMY、MDA、TNF-α和IL-6含量均显著升高（P<0.05）。结论：LPL基因敲除小鼠急性高脂血症性胰腺炎肺损伤更严重,其机制可能与LPL基因敲除引起更强的氧化应激和炎症有关。     

Effect of natural toxins and adipokinetic hormones on the activity of digestive enzymes in the midgut of the cockroach Periplaneta americana

This study examined the effect of two natural toxins (a venom from the parasitic wasp Habrobracon hebetor and destruxin A from the entomopathogenic fungus Metarhizium anisopliae), and one pathogen (the entomopathogenic fungus Isaria fumosorosea) on the activity of basic digestive enzymes in the midgut of the cockroach Periplaneta americana. Simultaneously, the role of adipokinetic hormones (AKH) in the digestive processes was evaluated. The results showed that all tested toxins/pathogens elicited stress responses when applied into the cockroach body, as documented by an increase of AKH level in the central nervous system. The venom from H. hebetor showed no effect on digestive enzyme activities in the ceca and midgut in vitro. In addition, infection by I. fumosorosea caused a decrease in activity of all enzymes in the midgut and a variable decrease in activity in the ceca; application of AKHs did not reverse the inhibition. Destruxin A inhibited the activity of all enzymes in the midgut but none in the ceca in vitro; application of AKHs did reverse this inhibition, and no differences between both cockroach AKHs were found. Overall, the results demonstrated the variable effect of the tested toxins/pathogens on the digestive processes of cockroaches as well as the variable ability of AKH to counteract these effects.     

Proteoglycan 4 deficiency protects against glucose intolerance and fatty liver disease in diet-induced obese mice

Objective

Proteoglycan 4 (Prg4) has emerged from human association studies as a possible factor contributing to weight gain, dyslipidemia and insulin resistance. In the current study, we investigated the causal role of Prg4 in controlling lipid and glucose metabolism in mice.