Colchicine administration to mice: a metabolic and ultrastructural study.

A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein-like particles which eventually transformed into lipid droplets. These ultrastructural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.     

The relationship between atherogenic index of plasma and epicardial adipose tissue in hemodialysis and peritoneal dialysis patients

Abstract

Introduction: Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between coronary artery disease and EAT was shown in end-stage renal disease (ESRD) patients. One of the established risk factor in this population is dyslipidemia. We aimed to determine the relationship between atherogenic index of plasma (AIP) and EAT in ESRD patients. Methods: This was a cross-sectional study involving 76 ESRD patients receiving PD or HD for ≥6 months and 42 healthy subjects. EAT was measured by using an electrocardiogram-gated 64-multidetector computed tomography (MDCT). Atherogenic index of plasma was calculated as the logarithmically transformed ratio of the serum trigliseride to HDL-cholesterol. Results: The etiology of ESRD patients was diabetic nephropathy (n?=?16), chronic glomerulonephritis (n?=?10), hypertensive nephropathy (n?=?23), polycystic kidney disease (n?=?7), nephrolithiasis (n?=?5) and unknown (n?=?15). There were no differences with respect to the following variables between ESRD patients and healthy subjects: age; sex; BMI; predialysis levels of DBP; serum levels of albumin, HDL-cholesterol and hemoglobin. However, ESRD patients had higher serum levels of trigliseride, hs-CRP and AIP when compared to healthy subjects. There was a statistically significant relationship between EAT, BMI and AIP in ESRD patients (r?=?0.42, p?<?0.001 and r?=?0.25, p?=?0.028, respectively). The stepwise linear regression analysis revealed that age, as well as BMI were independent predictors of EAT. Conclusion: We found a relationship between EAT as defined by MDCT and AIP in ESRD patients. Further clinical and experimental studies are needed.     

Influence of chronic stress on the compositions of hepatic cholesterol and triglyceride in male Wistar rats fed a high fat diet

Aim: We determined the influence of chronic stress (CS) on the compositions of hepatic cholesterol and triglyceride (TG) in rats fed a high fat diet (HFD). Methods: Male Wistar rats were fed either a standard diet or a HFD and half of the HFD fed rats were given CS (electric foot shock assisted with noise) for 8 weeks. Results: Compared with the control group, the levels of hepatic total cholesterol (TC) and TG were significantly elevated in the HFD and HFD with chronic stress (HFD+CS) groups, and the more severe elevations of them were found in the HFD group. Inversely, the more severe elevations of hepatic water‐soluble parts of TC and TG were found in the HFD+CS group, as the elevations of low‐density lipoprotein cholesterol, very low‐density lipoprotein cholesterol in liver and serum, tumor necrosis factor‐α, interleukin‐1β and malondialdehyde in liver. Meanwhile, downregulated mRNA expressions of hepatic liver X receptor‐α (LXR‐α) and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) were also more severe in the HFD+CS group. Conclusion: CS can aggravate the high levels of water‐soluble compositions of hepatic TC and TG induced by HFD as it aggravates hepatic inflammation and oxidative stress; in spite of that, however, it cannot further promote hepatic lipidosis. This is consistent with the downregulated mRNA expressions of LXR‐α and PPAR‐γ.     

Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice

Although the flavonoid tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone) is known to possess beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. Treatment with 100 μM tangeretin significantly increased the uptake of 2-NBDG in C2C12 myotubes. We also found that AMPK and AS160 were markedly phosphorylated by tangeretin treatment. In addition, pretreatment with an AMPK inhibitor significantly abrogated tangeretin-stimulated AS160 phosphorylation, glucose uptake, and Glut4 translocation from the cytosol to the plasma membrane. Furthermore, disruption of AMPK using siRNA transfection prevented the glucose uptake stimulated by tangeretin. We also examined the anti-diabetic properties of tangeretin in mice on HFD. Administration of HFD plus 200 mg/kg of tangeretin significantly altered weight gain, glucose tolerance, total cholesterol levels, and the secretion of adipocytokines, such as adiponectin, leptin, resistin, IL-6, and MCP-1. Moreover, AMPK was activated by 200 mg/kg of tangeretin in mouse muscle tissue, as expected from the cell system. These results suggest that tangeretin exerts anti-diabetic effects in both cell culture and mouse models, and these effects are necessary for activating AMPK.     

腹腔镜下袖状胃切除术治疗不同血脂水平肥胖患者的疗效研究

目的探讨在重度肥胖患者中,不同三酰甘油（TG）水平对减重效果及相关代谢指标的影响。方法回顾性收集2012年12月—2019年4月同济大学附属第十人民医院收治的行LSG手术的105例肥胖患者(BMI≥35kg/m2)的基线和术后6个月人体测量学指标和临床代谢指标。按基线TG水平分为TG正常组与TG异常组,两组间进行比较,并把腰围（WC）差值和臀围（HC）差值与各检测指标进行相关性分析（差值用Δ表示）。结果基线时,TG正常组空腹血糖（FPG）、餐后2h血糖（2hPG）、总胆固醇（TC）低于TG异常组（P<0.01）。术后6个月,两组多项代谢指标有明显改善,FPG及2hPG、TC无差异。与异常组相比,TG正常组的ΔBMI、ΔWC和ΔHC下降幅度更大。多元线性回归分析显示,TG正常组WC差值（ΔWC）与ΔBMI（r=0.765,P＜0.001）、颈围（NC）差值（ΔNC,r=0.394,P=0.021）、肌酐（Cr）差值（ΔCr,r=0.442,P=0.009）存在正相关,与ΔTC（r=-0.449,P=0.008）、高密度脂蛋白（HDL）差值（ΔHDL,r=-0.354,P=0.040）、低密度脂蛋白（LDL）差值（ΔLDL,r=-0.401,P=0.019）存在负相关。结论LSG能有效改善代谢紊乱情况。TG正常组WC和HC改善更显著,术前TG水平可作为LSG术后预测减重效果的指标之一。     

Association of apoE gene polymorphisms with lipid metabolism in renal diseases

Background and ObjectivesApolipoprotein E (apoE) plays a central role in the metabolism and homeostasis of lipids. ApoE gene encodes three major isoforms: ε2, ε3 a nd ε4 forming six phenotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Disorders of the lipid metabolism and the homeostasis are frequently coexist in renal diseases. The association between gene polymorphisms of apoE and lipid metabolism were not consistent. This meta-analysis was performed to assess the association between gene polymorphisms of apoE and lipid metabolism in renal diseases.MethodsA pre-defined literatures search and selection of eligible relevant investigations were performed to extract and collect data from electronic databases.ResultsSixteen articles were enrolled for the analysis of association between apoE gene polymorphisms and lipid metabolism. Subjects with E3E4 had a higher total cholesterol (TC) than those with E3E3, and subjects with E2E3 had a lower TC than those with E3E3. Subjects with ε2, had a lower TC than those with ε3 or ε4, and subjects with ε4 had a higher TC than those with, ε3. Subjects with E2E2, E2E3 or E4E4 had a higher triglyceride (TG) than those with E3E3. Subjects with ε4 had a higher TG than those with ε3. Subjects with ε2, had a higher level of TG than those with non-ε2. Subjects with E3E4 had a slightly lower high-density lipoprotein (HDL) than those with E3E3. E3E4 appeared to be associated with lower levels of HDL. Subjects with E2E2, E2E3 had a notably lower low-density lipoprotein (LDL) than those with E3E3. Subjects with ε2, had a lower LDL than those with ε3 or ε4 ApoE gene polymorphisms were not associated with very low-density lipoprotein, and lipoprotein (a) [Lp(a)]. Subjects with E2E3 or E2E4 had higher apoE levels than those with E3E3, and subjects with E4E4 had lower apoE levels than those with E3E3.ConclusionApoE gene polymorphisms are associated with the expression of TC, TG HDL, LDL, Lp(a) or apoE.     

Insulin resistance and depressed cardiac G6PD activity induced by glucocorticoid exposure during pregnancy are attenuated by maternal estrogen-progestin therapy

This study aimed to investigate the effects of maternal combined oral contraceptive (COC) on dams that were exposed to late gestational glucocorticoids (GC). Twenty-four pregnant female rats were randomly allotted into 4 groups of 6 dams each. Dams received COC (combination of 1.0 μg ethinylestradiol and 5.0 μg levonorgestrel p.o.) between 3rd and 11^th week after delivery with or without prior exposure to GC (dexamethasone; 0.2 mg/kg p.o.) that was administered between gestational days 14-19. Data showed that late-gestational GC exposure led to insulin resistance (IR), increased cardiac adenosine deaminase (ADA), xanthine oxidase (XO), lactate, lactate dehydrogenase (LDH), and disrupted cardiac glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defenses. On the other hand, maternal COC treatment in dams not exposed to gestational GC led to IR, increased cardiac XO, LDH and defective cardiac G6PD-dependent antioxidant defenses. However, maternal COC with prior gestational GC exposure led to attenuated IR, cardiac ADA, UA, LDH, and improved cardiac G6PD-dependent antioxidant defenses but worsened cardiac triglyceride (TG) accumulation when compared with dam with gestational GC exposure without maternal COC. Taken together, the findings of this study provide evidence that maternal COC treatment improves late gestational GC-programmed effects. This is however accompanied with enhanced cardiac TG accumulation.     

TyG指数与稳定性冠心病及冠状动脉钙化斑块负荷的相关性#br#

摘要：目的　探讨三酰甘油葡萄糖（TyG）指数与冠状动脉疾病（CAD）及冠状动脉钙化斑块负荷的相关性。方法　连续收集2015年9月—2017年6月承德医学院附属医院住院的符合纳入标准的疑似稳定性CAD的患者620例。根据冠状动脉CT血管造影（CCTA）结果将所有研究对象分为CAD组（n=449）和non-CAD组（n=171）。收集所有患者的临床资料,检查冠状动脉钙化（CAC）情况并进行冠状动脉钙化评分（CACS）。建立多因素二元Logistic回归模型,分析CAD和CAC的危险因素。结果　高TyG指数组CAD、2型糖尿病、血脂异常和CAC比例均较低TyG指数组高（均P＜0.05）。TyG指数与CACS呈正相关,与CAD危险因素心表面脂肪组织体积、心外膜脂肪组织体积、体质量指数等呈正相关,而与年龄和血清镁水平呈负相关（均P＜0.05）。除经典危险因素外,TyG指数≥8.23也是CAD和CAC的独立危险因素（P＜0.05）。结论　高TyG指数与冠状动脉粥样硬化斑块负荷及CAD患病相关,TyG指数升高是CAD和CAC的独立危险因素。