高浓度瘦素自分泌诱导脂肪细胞瘦素抵抗的研究

目的:观察高浓度瘦素对人脂肪细胞分解代谢及脂肪蓄积的直接影响,探讨瘦素自分泌调节在肥胖发生中的作用。方法:取正常成人皮下脂肪组织,常规提取和培养前脂肪细胞,待细胞融合后诱导分化为脂肪细胞后分为二组:低浓度组、高浓度组;分别培养于瘦素终浓度为100ng/ml、1000ng/ml的培养液a中。于培养48h、72h收集培养液检测游离脂肪酸和甘油的浓度,取脂肪细胞行油红O染色并图像分析计算脂肪细胞中脂肪颗粒的积分光密度。结果:与低浓度组相比,瘦素作用48h、72h后,高浓度组培养液中游离脂肪酸浓度均下降[(0.16711±0.011900)mmol/L VS(0.20589±0.008738)mmol/L,(0.17544±0.013920)mmol/L VS(0.23567±0.026220)mmol/L,甘油含量均减少(28.1733±0.91377)μmol/L VS(30.2456±0.30084)μmol/L,(28.9367±0.79530)μmol/L VS(31.8567±0.79024)μmol/L],而脂肪颗粒积分光密度则升高(461136.89±12049.947 VS418570.33±5668.129,441566.56±5921.602 VS 390133.67±7001.304)。结论:高浓度瘦素长时程作用脂肪细胞,可延缓脂肪分解代谢,增加脂肪蓄积。高浓度瘦素经自分泌诱导脂肪细胞产生瘦素抵抗,可能对肥胖发生有重要影响。     

瘦素对人前脂肪细胞增殖及分化的影响

目的 观察瘦索在体外对人前脂肪细胞增殖和分化的影响,探讨瘦素调节肥胖发生的可能机制.方法 分离并体外培养人腹部皮下前脂肪细胞.采用3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐（MTT）比色法、细胞计数法、油红O染色提取法及逆转录-聚合酶链式反应（RT-PCR）方法 分析不同浓度（0～1 000 ng/ml）瘦素对人前脂肪细胞增殖、脂质积聚及分化转录因子γ2过氧化物酶体增殖物激活受体（PPAR-γ）、CCAAT增强子α结合蛋白（C/EBP-α）mRNA表达的影响.结果 高浓度（1 000 ng/ml）瘦素能够促进人前脂肪细胞的增殖、脂质积聚以及PPAR-γ2、C/EBP-α mRNA表达（P〈0.05）.低浓度（10 ng/ml）和中浓度（100 ng/ml）瘦素对人前脂肪细胞的增殖及脂质积聚没有明显的促进作用（P〉0.05）.结论 在体外超生理浓度的瘦素能够促进前脂肪细胞的增殖和分化,提示瘦素抵抗、血清高瘦素浓度等病理状态时,瘦素可能促进前脂肪细胞的增殖及分化,影响肥胖发生.     

瘦素促进移植颗粒脂肪成活的实验研究

目的　探讨瘦素是否具有促进移植颗粒脂肪组织成活的作用。方法　取大鼠腹部皮下脂肪组织制成颗粒脂肪 ,分别用NS及 2 0ng ml瘦素处理后行自体头皮下移植。在不同观察时间取出移植组织称重 ,同时行HE及血管内皮细胞生长因子 (VEGF)染色。实验结果用SPSS统计分析软件进行统计学分析。结果　实验组和对照组比较 ,用瘦素处理的组织其周围包膜薄 ,脂肪细胞坏死融合少 ,重量维持率在移植 10、2 0、4 0d后分别为 10 8 3%、83 3%、6 6 3% ,和NS处理相应时间组6 0 0 %、4 2 1%、39 5 %的重量维持率相比 ,差异有显著性意义 (P <0 0 5 )。移植组织内VEGF染色强度较高。结论　瘦素对移植鼠颗粒脂肪组织具有促进成活作用 ,其作用机理可能是促进移植组织的血管增生。     

压应力对脂肪细胞活性的影响

目的 探讨压应力对脂肪细胞活性的影响,为提高自体脂肪移植的成活率及自体脂肪移植的临床应用提供参考.方法 将同等条件获取的脂肪颗粒随机分为5组,分别为对照组(0 kPa)、25 kPa组、50 kPa组、75 kPa组、100 kPa组,用自制的反馈式气控压应力细胞培养装置分别持续加压(对照组不予加压),于加压后1、2、3、4d,分别做葡萄糖转移实验,同时取加压4d后的脂肪颗粒做四甲基偶氮噻唑蓝(MTT)实验以及组织学HE染色,统计学分析比较各组脂肪颗粒活性的大小.结果 脂肪颗粒经不同大小压应力作用后,其转移葡萄糖的量随着压应力的增加而减少(P＜0.01),并且这种影响具有时间依赖性;MTT实验结果显示脂肪颗粒的吸光度值(A492nm)随压应力增 加而减少(P＜0.05),且与葡萄糖转移实验相关(r=0.838,P＜0.01);组织学切片提示脂肪细胞损伤率随压应力增加而增大(P＜0.01).结论 压应力会损伤脂肪颗粒的活性,建议在自体脂肪移植的临床应用中,在受区分离开阔的空间,以尽量减少压应力对脂肪颗粒活性的损伤.     

白细胞介素-1受体拮抗剂对兔椎间盘髓核前列腺素和5-羟色胺代谢的影响

目的:研究白细胞介素-1受体拮抗剂(IL-1Ra)对兔椎间盘髓核前列腺素E2(PGE2)、前列腺素F1琢(PGF1琢)和5-羟色胺(5-HT)代谢的影响。方法:取日本大白兔椎间盘髓核,制成匀浆后进行髓核组织的体外培养,观察不同浓度IL-1Ra和同一浓度IL-1Ra不同培养时间培养液中PGE2、PGF1琢和5-HT的含量。结果:IL-1Ra(100、200、400ng/ml)实验组较对照组培养液中PGE2、PGF1琢和5-HT的含量显著减少(P<0.01),呈现明显的浓度依赖性;IL-1琢(2.0ng/ml)组和IL-1Ra(200ng/ml)组随培养时间延长,PGE2、PGF1琢和5-HT的含量增加,每个时间段实验组与对照组浓度之差的差异有显著性意义(P<0.01)。结论:IL-1Ra可以拮抗IL-1琢对椎间盘髓核细胞PGE2、PGF1琢和5-HT合成的促进作用,呈现明显的浓度依赖性。IL-1Ra可以较长时间拮抗IL-1琢生物学作用,但本实验未能证明此作用具有时间依赖性。     

脂肪干细胞复合脂肪颗粒移植的实验研究

目的 探索脂肪来源干细胞(ADSCs)与脂肪颗粒复合移植对植入脂肪成活率的影响.方法 将1ml通过吸脂术获得的纯化脂肪颗粒分别与1ml含有下列细胞浓度的PBS混合:①原代ADSCs 1×106/ml(A组);②原代ADSCs 2×106/ml(B组);③二代ADSCs 2×106/ml(D组);④二代ADSCs 2×107/ml(E组);对照组为单纯的脂肪颗粒和1ml PBS混合移植(C组).随机注射移植于40只裸鼠背部皮下.移植12周后,取出移植物,进行如下测量:①大体观察;②重量和体积测定;③HE染色,观察细胞形态和小血管形成情况;④计算机图像分析测定血管密度;⑤统计学比较各实验组与对照组移植物体积、重量以及血管密度的差异.结果 ①湿重与体积:A、B、D、E组与C组之间差异有统计学意义(P ＜0.01);A组与B、D、E组之间差异有统计学意义(P ＜0.01);B、D、E组之间差异无统计学意义(P ＞0.05);②血管密度:A、B、D、E组与C组间差异有统计学意义(P ＜0.01);A、B、D、E各组间差异无统计学意义 (P ＞0.05).结论 原代和二代不同浓度的ADSCs与脂肪颗粒复合移植均可提高脂肪移植物成活率,相同浓度的原代与二代的ADSCs在促进脂肪颗粒成活上无显著差异,在一定范围内,随ADSCs浓度的增加,脂肪颗粒成活率也会相应提高;但是超过了一定范围,脂肪颗粒成活率不会随ADSCs浓度的增加而无限提高.     

针刺对肥胖大鼠下丘脑神经肽Y及脂肪蓄积的影响

目的:观察针刺对肥胖大鼠下丘脑神经肽Y及脂肪蓄积的影响,并探讨针刺减肥的治疗机理。方法:将60只SD大鼠造模后随机分为正常对照组、肥胖对照组及针刺治疗组,观察各组大鼠针刺治疗前、后的体重及Lee's指数。针刺治疗后取各组大鼠下丘脑常规免疫组织化学法检测神经肽Y表达,取脂肪组织染色后体视学方法测量体密度、数密度及表面积密度。结果:治疗后,针刺治疗组体重、Lee's指数与正常对照组无差异,与肥胖对照组相比明显减低(P<0.01);针刺治疗组下丘脑NPY积分光密度及脂滴体密度、表面积密度、数密度与肥胖对照组相比明显下降(P<0.01),与正常对照组相比无差异。结论:针刺治疗肥胖效果显著,且显著降低肥胖大鼠升高的下丘脑NPY含量,减少肥胖大鼠已增加的脂肪蓄积量。     

不同管径注射针对脂肪细胞活性的影响

目的检测不同管径注射针注射的脂肪细胞活性,研究注射针管径对脂肪细胞活性的影响。方法采用传统负压抽吸方式获得脂肪颗粒悬液200 ml;经双层纱布过滤并漂洗后,转入20支5 ml注射器,随机分为4组,每组5支注射器,其中1组为对照组。余3组以5 ml注射器连接不同管径注射针(12 G、16 G、18 G)匀速推出脂肪颗粒,每组分别注入5个15 ml离心管中。以Calcein-AM/Hoechst33342荧光染色法检测对照组及注射出的脂肪细胞活性,计算细胞成活率,比较注射针管径大小对脂肪细胞活性的影响。结果经12 G、16 G、18 G注射针注射过程顺利,无明显阻力。通过Calcein-AM/Hoechst33342染色法检测经不同管径注射针注射的脂肪颗粒中细胞成活率,对照组、12 G、16 G、18 G注射针管组细胞成活率分别为(83.53±7.92)%、(82.62±8.09)%、(75.78±10.94)%、(68.45±11.24)%,注射针管各组间差异具有统计学意义(P0.05),12 G注射针管组细胞成活率与对照组差异无统计学意义(P0.05)。结论单位时间内注射一定量的脂肪颗粒随着注射针管内径减小,脂肪颗粒细胞成活比将随之降低,增大注射针管径可增高注射后细胞成活比。     

绝经后骨质疏松症妇女血清痩素水平与骨密度的关系

目的 观察绝经后骨质疏松症妇女血清瘦素水平与骨密度(BMD)、骨矿含量(BMC)的相关性。方法 ELISA法检测32名绝经后骨质疏松症妇女(绝经组)和27名体重指数(BMI)相匹配的非绝经正常对照者(非绝经组)的空腹血清瘦素浓度,双能X线骨密度仪测定受试者腰椎BMD、BMC、T值、Z值。结果 绝经组和非绝经组的血清瘦素浓度分别为12.43±7.90ng/ml和11.76±4.42ng/ml,两组之间无差异;两组血清瘦素浓度均与体重、BMI和脂肪含量(Fat％)显著正相关,绝经组的瘦素水平与BMD及BMC无相关性,非绝经组瘦素浓度与BMDIL3和BMCL5相关(r=0.132,P<0.05;r=0.140,P<0.05),但调整BMI后瘦素浓度与BMD及BMC:的相关性消失(r=0.079,P>0.05;r=0.067,P>0.05)。结论成年妇女瘦素水平与体重、体脂及脂肪含量显著相关,瘦素不是绝经后妇女骨质疏松症的主要影响因素。     

白术挥发油对LNCaP与DU145细胞表达性激素和PSA等指标的影响及意义

目的 研究白术挥发油对人前列腺癌细胞株的体外抗肿瘤作用. 方法 常规培养LNCaP和DU145细胞株.设4个对照组:不含血清的空白培养液(A组),含血清的培养液(B组),含血清培养LNCaP细胞(C组),含血清培养DU145细胞(D组).设6个实验组,C组加入白术挥发油浓度分别50 μg/ml(C1组)、250 μg/ml(C2组)及500 μg/ml(C3组),D组分别加入上述3种浓度的白术挥发油(D1组、D2组、D3组).10组细胞铺24孔板,每组均设3个复孔,两种细胞均分别按每孔2×106铺板.常规培养48 h后,6个实验组加入各自浓度的白术挥发油,4个对照组以等量培养液替代.电镜观察各组细胞凋亡现象,取各组培养液上清并冷离心收集标本,分别检测睾酮(T)、雌二醇(E2)、孕酮(P)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(b-FGF)、tPSA和fPSA浓度.实验数据行多样本比较的统计学分析. 结果 C1和D2组生长抑制效应较好,LNCaP细胞呈时间效应正比关系,但DU145细胞仅在药物作用24 h后达到一次抑制率最大化(60.96％).与对照组相比,C、D组T浓度均为0,E2分别为269 pg/ml和239.81 pg/ml,呈高表达(P＜0.05);P组间变化差异不显著;VEGF、b-FGF和fPSA均呈高表达,2组分别为102.96 pg/ml、0.26 ng/ml、0.16 ng/ml和1763.40 pg/ml、6.41 ng/ml、0.44 ng/ml,以D组更明显(P ＜0.05);tPSA分别为0.36 ng/ml和0.发生凋亡的C1、C2、C3和D3组中,T最高由0升至0.37 ng/ml; E2最高由239.81 pg/ml升至649.90 pg/ml(P＜0.05);P最高由0.98 ng/ml升至9.83 ng/ml(P＜ 0.01).VEGF、b-FGF和fPSA呈总体下降趋势.C2和D2组fPSA分别由0和0.04 ng/ml升至1.78 ng/ml和0.23 ng/ml. 结论 白术挥发油对人前列腺癌细胞具有一定的凋亡诱导作用.雄激素非依赖性DU145细胞在性激素、细胞因子和PSA等表达方面与雄激素依赖性LNCaP细胞有不同的特点.     

The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes

HIV protease inhibitors (HPIs) are potent antiretroviral agents clinically used in the management of HIV infection. Recently, HPI therapy has been linked to the development of a metabolic syndrome in which adipocyte insulin resistance appears to play a major role. In this study, we assessed the effect of nelfinavir on glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. An 18-h exposure to nelfinavir resulted in an impaired insulin-stimulated glucose uptake and activation of basal lipolysis. Impaired insulin stimulation of glucose up take occurred at nelfinavir concentrations >10 micromol/l (EC(50) = 20 micromol/l) and could be attributed to impaired GLUT4 translocation. Basal glycerol and free fatty acid (FFA) release were significantly enhanced with as low as 5 micromol/l nelfinavir, displaying fivefold stimulation of FFA release at 10 micromol/l. Yet, the antilipolytic action of insulin was preserved at this concentration. Potential underlying mechanisms for these metabolic effects included both impaired insulin stimulation of protein kinase B Ser 473 phosphorylation with preserved insulin receptor substrate tyrosine phosphorylation and decreased expression of the lipolysis regulator perilipin. Troglitazone pre- and cotreatment with nelfinavir partly protected the cells from the increase in basal lipolysis, but it had no effect on the impairment in insulin-stimulated glucose uptake induced by this HPI. This study demonstrates that nelfinavir induces insulin resistance and activates basal lipolysis in differentiated 3T3-L1 adipocytes, providing potential cellular mechanisms that may contribute to altered adipocyte metabolism in treated HIV patients.     

急性胰腺炎发作后促炎细胞因子在诱导脂肪分解中的作用

[摘 要] 目的 研究急性胰腺炎（acute pancreatitis,AP）发作后出现糖代谢异常患者的脂代谢指标与促炎细胞因子之间的相关性,探讨急性胰腺炎发作后促炎细胞因子在诱导脂肪分解中的作用。方法 选取2015年2月至2017年2月间宝鸡市人民医院收治的急性胰腺炎患者98例,根据急性胰腺炎发作后是否存在糖代谢异常将其分成糖代谢异常（abnormal glucose metabolism,AGM）组（28例）和糖代谢正常（normalglucose metabolism,NGM）组（70例）两组,检测患者白介素6（IL-6）、肿瘤坏死因子（TNF-α）等促炎细胞因子和甘油三脂（TG）、甘油（Glycerol）、总胆固醇（TC）、游离脂肪酸（FFA）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、载脂蛋白B（Apo-B）等脂代谢指标,在控制年龄、性别、病情程度及吸烟等变量后对促炎细胞因子和脂代谢指标进行线性回归分析,以了解其相互关系。结果 急性胰腺炎发作后AGM组患者的血浆甘油水平随IL-6水平的升高而增加103.4%（P=0.021）,而游离脂肪酸随IL-6水平升高而减少7.2%（P=0.005）。此外,AGM组患者的血浆甘油三脂水平随TNF-α的增加而减少134.1%（P=0.025）,但游离脂肪酸水平随TNF-α水平升高而增加314.2%（P=0.025）。但NGM组患者的各脂质代谢指标与IL-6及TNF-α无明显相关（P > 0.05）。结论 促炎因子诱导的脂肪分解可能是急性胰腺炎发作后糖代谢异常的重要发病机制,其中促炎细胞因子IL-6和TNF-α作为急性胰腺炎发作后脂肪分解的驱动节点,这种调制或控制脂肪分解可能成为一种新兴的糖尿病治疗方式。     

Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice.

Recent studies have shown that genetic deficiency of the adipocyte fatty acid-binding protein (aP2) results in minor alterations of plasma lipids and adipocyte development but provides significant protection from dietary obesity-induced hyperinsulinemia and insulin resistance. To identify potential mechanisms responsible for this phenotype, we examined lipolysis and insulin secretion in aP2-/- mice. Beta-adrenergic stimulation resulted in a blunted rise of blood glycerol levels in aP2-/- compared with aP2+/+ mice, suggesting diminished lipolysis in aP2-/- adipocytes. Confirming this, primary adipocytes isolated from aP2-/- mice showed attenuated glycerol and free fatty acid (FFA) release in response to dibutyryl cAMP. The decreased lipolytic response seen in the aP2-/- mice was not associated with altered expression levels of hormone-sensitive lipase or perilipin. The acute insulin secretory response to beta-adrenergic stimulation was also profoundly suppressed in aP2-/- mice despite comparable total concentrations and only minor changes in the composition of systemic FFAs. To address whether levels of specific fatty acids are different in aP2-/- mice, the plasma FFA profile after beta-adrenergic stimulation was determined. Significant reduction in both stearic and cis-11-eicoseneic acids and an increase in palmitoleic acid were observed. The response of aP2-/- mice to other insulin secretagogues such as arginine and glyburide was similar to that of aP2+/+ mice, arguing against generally impaired function of pancreatic beta-cells. Finally, no aP2 expression was detected in isolated pancreatic islet cells. These results provide support for the existence of an adipo-pancreatic axis, the proper action of which relies on the presence of aP2. Consequently, aP2's role in the pathogenesis of type 2 diabetes might involve regulation of both hyperinsulinemia and insulin resistance through its impact on both lipolysis and insulin secretion.     

Transferrin and iron contribute to the lipolytic effect of serum in isolated adipocytes

Previous reports have demonstrated that normal serum can increase the rate of adipocyte lipolysis in vitro. However, the nature of the lipolytic activity has remained obscure. We have investigated the lipolytic activity of human serum using isolated rat adipocytes. Human serum resulted in a dose-dependent stimulation of lipolysis (glycerol release) in adipocytes, with a half-maximal effective dose of 0.05% serum and with maximal stimulation with 1% serum. The effect of serum on glycerol release was rapid (within 30 min), and the effect was reversible. Partial purification of this lipolytic activity using gel filtration and ion-exchange chromatography demonstrates that a protein of approximately 80 kDa contributes to the lipolytic activity. Human transferrin mimicked the activity of partially purified serum, resulting in a maximal 50% increase in basal lipolysis. In addition, ferrous sulfate heptahydrate induced a biphasic increase in the rate of lipolysis, with a maximal increase of 50% at approximately 0.6 microg/ml iron. Inhibitors of protein kinase A (H89) and mitogen-activated protein kinase (PD98059) did not block the effect of serum on lipolysis, whereas the free radical scavenger N-acetyl-l-cysteine completely inhibited the effect. These findings suggest that the stimulatory effect of serum on lipolysis is in part mediated by iron, probably through a prooxidant mechanism.     

Endotoxin influence on lipolysis in isolated human and primate adipocytes.

The influence of E. coli endotoxin on basal and norepinephrine-stimulated lipolysis as well as on cyclic AMP accumulation was studied in human and rhesus monkey adipocytes. The effect of indomethacin on lipolysis was also investigated.Human and rhesus adipocytes exhibited qualitatively similar responses to norepinephrine (0.59–11.8 μM). There was a positive correlation between cell volume and basal lipolysis in human, but not in rhesus, cells. A positive correlation was also noted between cell volume and the response to endotoxin and to norepinephrine in human cells. The increment in response to norepinephrine after endotoxin treatment, however, was negatively correlated to basal lipolysis.Endotoxin (0.32 μg/0.5 ml of cell suspension) increased basal free fatty acid release and significantly enhanced norepinephrine-stimulated glycerol release from rhesus adipocytes. In human fat cells, basal release of glycerol was stimulated by endotoxin at all concentrations used, whereas basal FFA release was increased at endotoxin concentrations of 0.032 and 0.320 μg/0.5 ml of cell suspension. Endotoxin significantly depressed norepinephrine-stimulated release of FFA at all endotoxin concentrations without significantly influencing concurrent glycerol release.Treatment of rhesus fat cells with endotoxin and endotoxin plus indomethacin resulted in significant increases in cAMP content. In human fat cells, endotoxin alone did not influence cAMP concentration; however, exposure to norepinephrine or to endotoxin plus indomethacin resulted in significantly increased levels of cAMP.     

痩素对小鼠破骨细胞分化及功能的影响

目的 观察瘦素（leptin）对体外骨髓诱导培养的小鼠破骨细胞分化和功能的作用效应,探索leptin和骨吸收之间的关联.方法 建立由巨噬细胞集落刺激因子（M-CSF）和骨保护素配体（RANKL）为共同细胞因子的小鼠破骨细胞骨髓诱导培养体系,将不同浓度的leptin作用于破骨细胞.实验中根据培养液中是否加入M-CSF和RANKL并依据leptin浓度的不同分为：A组,M-CSF和RANKL;B组,M-CSF、RANKL和leptin（80 ng/ml）;C组,M-CSF、RANKL和leptin（160 ng/ml）;D组,M-CSF、RANKL和leptin（240 ng/ml）;E组,M-CSF、RANKL和leptin（320 ng/ml）;F组,M-CSF、RANKL和leptin（400 ng/ml）;同时设立空白对照组G组.于作用后第7天取细胞玻片进行抗酒石酸酸性磷酸酶（TRAP）染色,观察破骨细胞并计数;于第10天取出骨片进行甲苯胺蓝染液染色,在光镜和扫描电镜观察骨吸收陷窝形态.结果：诱导培养的小鼠破骨细胞形态特征明显;A组在破骨细胞数量与D、E、F组相比较有明显的统计学差异（P＜0.05）;A组骨吸收面积比与B、C、D、E、F组都有明显的统计学差异（P＜0.05）.结论：leptin抑制体外培养的破骨细胞的分化和骨吸收功能.     

Evidence for a major role of skeletal muscle lipolysis in the regulation of lipid oxidation during caloric restriction in vivo.

A lipolytic process in skeletal muscle has recently been demonstrated. However, the physiological importance of this process is unknown. We investigated the role of skeletal muscle lipolysis for lipid utilization during caloric restriction in eight obese women before and after 11 days of very low-calorie diet (VLCD) (2.2 MJ per day). Subjects were studied with indirect calorimetry and microdialysis of skeletal muscle and adipose tissue in order to analyze substrate utilization and glycerol (lipolysis index) in connection with a two-step euglycemic-hyperinsulinemic (12 and 80 mU/m(2). min) clamp. Local blood flow rates in the two tissues were determined with (133)Xe-clearance. Circulating free fatty acids and glycerol decreased to a similar extent during insulin infusion before and during VLCD, and there was a less marked insulin-induced reduction in lipid oxidation during VLCD. Adipose tissue glycerol release was hampered by insulin infusion to the same extent ( approximately 40%) before and during VLCD. Skeletal muscle glycerol release was not influenced by insulin before VLCD. However, during VLCD insulin caused a marked (fivefold) (P < 0.01) increase in skeletal muscle glycerol release. The effect was accompanied by a fourfold stimulation of skeletal muscle blood flow (P < 0.01). We propose that, during short-term caloric restriction, the reduced ability of insulin to inhibit lipids, despite a preserved antilipolytic effect of the hormone in adipose tissue, is caused by an augmented mobilization of fat from skeletal muscle, and that a physiological role of muscle lipolysis provides a local source of fatty acids.     

Plasma Levels of Catecholamines and Lipolysis During Starvation in Growing Pigs

The aim of this study was to clarify the triggering mechanism of lipolysis in adipose tissue during feed withdrawal in pigs. Evaluation of blood samples drawn via an intravenous catheter from 10 growing pigs fasted for 60 h demonstrated, in addition to a haemodilution, a significant rise in plasma levels of non-esterified fatty acids (250 ± 37 to 1427 ± 144 μmol/l) and free glycerol (98 ± 27 to 232 ± 41 μmol/l) within 48 h of feed restriction, and thereafter the concentrations levelled off. The pigs also showed a significant decrease in plasma levels of glucose (6.01 ± 0.20 to 4.62 ± 0.12 mmol/l) within 48 h of fasting, followed by repeated increase until the end of the experimental period. A significant decrease in plasma insulin-like growth factor I (84 ± 13 to 65 ± 7 ng/ml) was observed after 16 h, which continued during the whole period of feed withdrawal. However, no significant changes in plasma levels of adrenaline and noradrenaline during the period of increased lipolysis were detected. Therefore, the observed stimulation of lipolysis in growing swine during fasting is not the result of an increase in plasma concentration of catecholamines.     

Epidural blockade suppresses lipolysis during major abdominal surgery

BACKGROUND AND OBJECTIVES: The purpose of the study was to investigate the effect of thoracic epidural administration of local anesthetic, i.e., epidural block on perioperative lipolysis. METHODS: Fourteen patients undergoing elective colorectal surgery were randomly assigned to receive either general anesthesia combined with epidural block (EDA, n = 7) or general anesthesia alone (control, n = 7). The rates of glycerol appearance (R(a) glycerol), i.e., lipolysis, were assessed by the stable isotope tracer [1,1,2,3,3-(2)H(5)]glycerol before, during, and 2 hours after the operation. Plasma concentrations of metabolic substrates (glycerol, free fatty acids [FFA], lactate) and hormones (insulin, glucagon, cortisol) were also determined. RESULTS: In the EDA group, R(a) glycerol decreased to lower intra- and postoperative values than in the control group (P <.05). Perioperative plasma concentrations of glycerol, FFA, lactate, and insulin remained unaltered with both anesthetic techniques. Intraoperative plasma glucagon and cortisol concentrations were lower in the EDA group than in the control group (P <.05). CONCLUSIONS: Epidural block suppresses lipolysis during and 2 hours after major abdominal surgery without affecting plasma glycerol or FFA concentrations.