Modulation of carbohydrate metabolism and peptide hormones by soybean isoflavones and probiotics in obesity and diabetes

Soybean and its isoflavones have been shown to have beneficial effects on carbohydrate and lipid metabolism and on renal function. Probiotics may potentiate the beneficial effects of isoflavones by converting the inactive isoflavone glycoside to aglycones, which are biologically active, thereby producing a synergistic effect. We therefore studied the effects of soybean isoflavones in the presence and absence of probiotics on glucose and triglyceride metabolism and the peptide hormones involved in their metabolism. Lean and obese SHR/N-cp rats were fed AIN-93 diets containing 0.1% soybean isoflavone mixture, 0.1% probiotics mixture or both. Plasma was analyzed for glucose, triglycerides, parameters of renal function and peptide hormones -- insulin, leptin, glucagon and ACTH -- that are involved in glucose and lipid metabolism. Isoflavones given alone lowered plasma glucose in both phenotypes while triglyceride was decreased only in lean animals. Isoflavones also lowered aspartate amino transferase and alanine amino transferase in both phenotypes. Isoflavones had significant effect on plasma insulin, leptin and glucagon in lean rats but not in obese rats. Thus, our data show that in lean animals, isoflavones have hypoglycemic and hypolipidemic effect, and the effect is mediated by changes in peptide hormones. When lipid levels are very high as in obese rats, isoflavones fail to lower plasma triglyceride levels. Probiotics do not appear to enhance the effect of isoflavones.     

大豆异黄酮对游泳小鼠能量代谢的影响

目的：探讨大豆异黄酮（SI）对游泳小鼠能量代谢的影响。方法：建立小鼠运动疲劳模型,选用雄性昆明小鼠30只,根据体质量随机分为3组（n=10）：正常组、游泳模型组、游泳+SI干预组（SI组）。正常组及模型组小鼠以AIN-93M合成饲料饲养,SI组在AIN-93M合成饲料中添加相应剂量的SI （4 g/kg）。饲养2周后,模型组和SI组小鼠负重2%游泳1 h后处死,测定其血乳酸（Lac）含量及乳酸脱氢酶（LDH）、琥珀酸脱氢酶（SDH）、肌酸激酶（CK）、ATP酶的活性。结果：与正常组相比,模型组和SI组血清中Lac含量明显增加（P<0.05）,模型组肌肉和SI组血中LDH活性显著升高（P<0.05）,模型组血清、肝脏和肌肉中SDH和CK活性明显升高,SI组血清和肌肉中SDH和CK活性显著升高（P<0.05）;与模型组相比,SI组小鼠游泳后,血清Lac含量明显下降（P<0.05）,LDH、SDH、CK酶活性较模型组都有明显升高（P<0.05）。结论：大豆异黄酮对游泳小鼠能量代谢具有一定的调节作用。     

Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia

Hyperhomocysteinemia (HHCY) is a consequence of impaired methionine/cysteine metabolism and is caused by deficiency of vitamins and/or enzymes such as cystathionine beta-synthase (CBS). Although HHCY is an important and independent risk factor for cardiovascular diseases that are commonly associated with hepatic steatosis, the mechanism by which homocysteine promotes the development of fatty liver is poorly understood. CBS-deficient (CBS(-/-)) mice were previously generated by targeted deletion of the Cbs gene and exhibit pathological features similar to HHCY patients, including endothelial dysfunction and hepatic steatosis. Here we show abnormal lipid metabolism in CBS(-/-) mice. Triglyceride and nonesterified fatty acid levels were markedly elevated in CBS(-/-) mouse liver and serum. The activity of thiolase, a key enzyme in beta-oxidation of fatty acids, was significantly impaired in CBS(-/-) mouse liver. Hepatic apolipoprotein B100 levels were decreased, whereas serum apolipoprotein B100 and very low density lipoprotein levels were elevated in CBS(-/-) mice. Serum levels of cholesterol/phospholipid in high density lipoprotein fractions but not of total cholesterol/phospholipid were decreased, and the activity of lecithin-cholesterol acyltransferase was severely impaired in CBS(-/-) mice. Abnormal high density lipoprotein particles with higher mobility in polyacrylamide gel electrophoresis were observed in serum obtained from CBS(-/-) mice. Moreover, serum cholesterol/triglyceride distribution in lipoprotein fractions was altered in CBS(-/-) mice. These results suggest that hepatic steatosis in CBS(-/-) mice is caused by or associated with abnormal lipid metabolism.     

Effects of genetic and diet-induced obesity on lipid metabolism

C57BL/6J obese (ob/ob) and lean mice fed ad libitum on a normal mouse chow diet (Normal), were compared with lean mice of the same age and strain fed ad libitum on a high-fat diet, consisting of the Normal diet with the addition of beef lard (Lard), from age 3 months for 34 days. The lard-fed mice were seen to have significantly higher (P<0.05) body weight in this 34-day period than that of the other two groups fed on the Normal diet. Epididymal fat depot and adipocyte cell size were significantly larger (P<0.05) in the Lard-fed lean mice and in the obese (ob/ob) mice than were those of the Normal-fed lean mice. Dietary Lard intake did not significantly affect concentrations of plasma triglyceride although those of plasma cholesterol were significantly increased (P<0.05). The development of obesity in these Lard-fed mice appeared to be accelerated and significant.     

Physical exercise mitigates high-fat diet-induced adiposopathy and related endocrine alterations in an animal model of obesity

The dysregulation of adipokine secretion owing to adiposopathy can contribute to the pathogenesis of obesity-related disorders. Being that exercise is an advised strategy against obesity-induced adiposopathy, we aimed to analyze the role of physical exercise as a preventive and therapeutic strategy against high-fat diet (HFD)-induced adipokine and ghrelin alterations. Rats were pair-fed the Lieber De Carli standard diet (S, 35 Kcal% fat) or HFD (71 Kcal% fat) over 17 weeks. Animals were assigned into four groups as follows: standard diet sedentary (SS), standard diet voluntary physical activity (SVPA), high-fat diet sedentary (HS), and high-fat diet voluntary physical activity (HVPA). After 9 weeks of dietary treatment, half of the SS and HS animals were submitted to an 8-week endurance training program, standard diet endurance training (SET), and high-fat-diet endurance training (HET) groups, maintaining the respective diets. Although there were no changes in body weight, HFD increased visceral adiposity, percentage of large adipocytes, hypoxia inducible factor (HIF)-1α, and leptin contents in epididymal adipose tissue (eWAT) and decreased plasma content of adiponectin (AdipQ). Both VPA and ET decreased visceral adiposity and percentage of large adipocytes in HFD-fed animals, but ET also increased the percentage of small- to medium-sized adipocytes. VPA increased plasma growth hormone secretagogue receptor (GHS-R) and decreased leptin protein in HVPA group. ET decreased plasma insulin and leptin levels and eWAT HIF-1α and leptin expression in HET group. Moreover, ET improved insulin sensitivity, plasma high molecular weight, and AdipQ and ghrelin levels and increased eWAT and GHS-R expression. Our data suggest that exercise, particularly ET, reverted adiposopathy and related endocrine alterations induced by an isocaloric HFD pair-fed diet.     

Effects of soybean beta-conglycinin on hepatic lipid metabolism and fecal lipid excretion in normal adult rats

beta-Conglycinin decreased blood triacylglycerol (TAG) levels in male Wistar adult rats. Liver mitochondrial carnitine palmitoyltransferase activity in the beta-conglycinin-fed group significantly increased as against the casein-fed group. Hepatic fatty acid synthase activity in the beta-conglycinin group significantly decreased as against that of the casein-fed group. Fecal fatty acid excretion in the beta-conglycinin group was significantly higher than in the casein group.     

Scanning electron microscopic analysis of intramyocellular lipid droplets in an animal model of type 2 diabetes

Objective: To evaluate the accumulation pattern of intramyocellular lipids (IMCLs) in striated muscle during the development and progression of diabetes, using a novel scanning electron microscopic method. Methods and Procedures: Hyperglycemia was induced by feeding diabetes‐prone (DP) Psammomys obesus a high‐energy (HE) diet. Lipid accumulation within gastrocnemius muscle fibers was assessed in formalin‐fixed muscle samples during the development of hyperglycemia using high resolution imaging in a scanning electron microscope. We evaluated the temporal relationship between changes in IMCL quantity and morphology and the altered glucose metabolism and assessed the effect of reversal of hyperglycemia on IMCL level and morphology. Diabetes‐resistant (DR) P. obesus served as controls. Results: Lipid accumulation in the muscle fibers of DP animals was increased with the development of hyperglycemia. This was characterized by increased lipid density as well as by an abundance of large lipid droplets. Reversal of the phenotype resulted in the disappearance of large lipid droplets. The IMCL level and the distribution of lipid droplet size were similar in muscles of both the normoglycemic DR and DP animals, with an abundance of small lipid droplets. This profile was changed following a HE diet only in the DP animals. Discussion: Lipid accumulation in the muscle of P. obesus during the development of hyperglycemia is characterized by increased quantity and accumulation of large lipid droplets. These changes were reversible upon normalization of blood glucose. The evaluated methodology is a useful tool for the study of the dynamics of lipid accumulation in different metabolic conditions.     

干旱胁迫对苗期大豆异黄酮合成的影响

以不同耐旱性的2个大豆品种(高耐旱JP-6、低耐旱JP-16)为研究材料,采用高效液相色谱和实时荧光定量PCR技术,分析不同时间持续干旱胁迫下,大豆叶片和根系中异黄酮的积累变化及关键酶基因的表达情况.结果表明:大豆根部异黄酮含量显著高于叶部,而异黄酮关键酶基因的表达量则在叶片中更高,耐旱品种JP-6根部的异黄酮积累量更大.随着干旱胁迫持续时间的增加,不同耐旱品种的异黄酮合成与积累变化规律存在显著差异:强耐旱品种JP-6的根和叶中,异黄酮积累量均呈现先下降后升高的趋势;而弱耐旱品种JP-16则相反,异黄酮积累量在不同部位中均呈现先上升后降低的趋势;除JP-6叶中C4H、4CL、IFS2等异黄酮合成上游基因外,其他不同品种、不同部位的关键酶基因表达量均随着干旱胁迫持续时间的增加,呈现先下降后上升的趋势.大豆叶片是异黄酮的主要合成部位,大豆根部也存在少量的异黄酮合成.弱耐旱大豆根部的异黄酮合成和最终积累量均较低,强耐旱品种则较高.根部异黄酮积累量高的大豆品种,其耐旱性更强.     

Effects of dietary soybean lecithin on plasma lipid transport and hepatic cholesterol metabolism in rats

Dietary lecithin can stimulate bile formation and biliary lipid secretion, particularly cholesterol output in bile. Studies also suggested that the lecithin-rich diet might modify hepatic cholesterol homeostasis and lipoprotein metabolism. Therefore, we examined hepatic activities of 3-hydroxy-3 methylglutaryl coenzyme A reductase "HMG -CoA reductase", cholesterol 7 alpha-hydroxylase and acyl-CoA: cholesterol acyltransferase "ACAT" as well as plasma lipids and lipoprotein composition in rats fed diets enriched with 20% of soybean lecithin during 14 days. We also evaluated the content of hepatic canalicular membrane proteins involved in lipid transport to the bile (all P-glycoproteins as detected by the C 219 antibody and the sister of P-glycoprotein "spgp" or bile acid export pump) by Western blotting. As predicted, lecithin diet modified hepatic cholesterol homeostasis. The activity of hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase was enhanced by 30 and 12% respectively, while microsomal ACAT activity showed a dramatic decrease of 75%. As previously reported from ACAT inhibition, the plasma level and size of very low-density lipoprotein (VLDL) were significantly decreased and bile acid pool size and biliary lipid output were significantly increased. The canalicular membrane content of lipid transporters was not significantly affected by dietary lecithin. The current data on inhibition of ACAT activity and related metabolic effects by lecithin mimic the previously reported effects following drug-induced inhibition of ACAT activity, suggesting potential beneficial effects of dietary lecithin supplementation in vascular disease.     

利拉鲁肽联合二甲双胍对肥胖合并2型糖尿病患者糖脂代谢、胰岛β细胞功能及体脂的影响探究

目的探讨利拉鲁肽联合二甲双胍对肥胖合并2型糖尿病患者糖脂代谢、胰岛β细胞功能及体脂的影响。 方法选择成都市郫都区第二人民医院2017年1月至2018年12月收治的肥胖合并2型糖尿病患者141例作为研究对象,按照随机数字表法分为利拉鲁肽组47例、二甲双胍组47例与联合组47例。利拉鲁肽组采用利拉鲁肽治疗,二甲双胍组采用二甲双胍治疗,联合组采用利拉鲁肽联合二甲双胍治疗。三组疗程均为3个月。比较三组治疗前后糖代谢、脂代谢、胰岛β细胞功能和体重指数（BMI）变化,及不良反应,治疗前后比较采用配对t检验,三组间比较采用F检验,两组间比较采用LSD-t检验。 结果三组治疗后FPG、HbA1c和2hPG水平较治疗前降低,差异具有统计学意义（P均< 0.05）;联合组治疗后FPG（6.57±0.39）?mmol/L、HbA1c（7.03±0.42）%和2hPG（8.78±0.45）mmol/L低于利拉鲁肽组（7.03±0.32）mmol/ L、（7.68±0.35）%、（9.56±0.65）mmol/L（t = 6.251、8.151、6.764,P均?< 0.05）和二甲双胍组（7.06±0.39）mmol/L、（7.76±0.46）%、（9.70±0.81）?mmol/L,差异具有统计学意义（t = 6.091、8.034、6.807,P均< 0.05）。三组治疗后HDL-C水平较治疗前升高,而TC、LDL-C和TG水平较治疗前降低,差异具有统计学意义（P均< 0.05）;联合组治疗后HDL-C （1.56±0.13） mmol/ L高于利拉鲁肽组（1.29±0.14） mmol/ L（t = 9.689,P < 0.05）和二甲双胍组（1.32±0.15） mmol/ L,差异具有统计学意义（t = 8.289,P < 0.05）;而联合组TC（4.35±0.38） mmol/L、LDL-C（2.79±0.21）mmol/L和TG（2.15±0.26） mmol/ L低于利拉鲁肽组（5.18±0.43）mmol/L、（3.19±0.15）mmol/L、（2.65±0.17） mmol/L（t = 9.916、10.626、11.035,P < 0.05）和二甲双胍组（5.15±0.34）mmol/L、（3.23±0.25）mmol/ L、（2.68±0.23） mmol/ L,差异具有统计学意义（t = 10.756、9.239、10.467,P均< 0.05）。三组治疗后HOMA-β较治疗前升高,差异具有统计学意义（P < 0.05）;联合组治疗后HOMA-β（4.87±0.28）高于利拉鲁肽组（4.15±0.36）和二甲双胍组（4.08±0.41）,差异具有统计学意义（t = 10.823,10.909,P均< 0.05）。三组治疗后BMI较治疗前降低,差异具有统计学意义（P < 0.05）;联合组治疗后BMI （28.08±0.37）kg/m²低于利拉鲁肽组（29.73±0.49）kg/m²和二甲双胍组（29.61±0.43）kg/m²,差异具有统计学意义（t = 18.423,18.490,P均< 0.05）。 结论利拉鲁肽联合二甲双胍对肥胖合并2型糖尿病患者效果良好,可改善患者糖脂代谢和胰岛β细胞功能,降低体质指数,值得临床借鉴。     

Effects of soybean isoflavones on the growth performance,intestinal morphology and antioxidative properties in pigs

Soybean meal is rich in soybean isoflavones, which exhibit antioxidant, anti-inflammatory, antiviral and anticancer functions in humans and animals. This study was conducted to investigate the effects of soybean isoflavones on the growth performance, intestinal morphology and antioxidative properties in pigs. A total of 72 weaned piglets (7.45 ± 0.13 kg; 36 males and 36 females) were allocated into three treatments and fed corn-soybean meal (C-SBM), corn-soy protein concentrate (C-SPC) or C-SPC supplemented with equal levels of the isoflavones found in the C-SBM diet (C-SPC + ISF) for a 72-day trial. Each treatment had six replicates and four piglets per replicate, half male and half female. On day 42, one male pig from each replicate was selected and euthanized to collect intestinal samples. The results showed that compared to pigs fed the C-SPC diet, pigs fed the C-SBM and C-SPC + ISF diets had higher BW on day 72 (P < 0.05); pigs fed the C-SBM diet had significantly higher average daily gain (ADG) during days 14 to 28 (P < 0.05), with C-SPC + ISF being intermediate; pigs fed the C-SBM diet tended to have higher ADG during days 42 to 72 (P = 0.063), while pigs fed the C-SPC + ISF diet had significantly higher ADG during days 42 to 72 (P < 0.05). Moreover, compared to pigs fed the C-SPC diet, pigs fed the C-SBM diet tended to have greater villus height (P = 0.092), while pigs fed the C-SPC + ISF diet had significantly greater villus height (P < 0.05); pigs fed the C-SBM and C-SPC + ISF diets had significantly increased villus height-to-crypt depth ratio (P < 0.05). Compared with the C-SPC diet, dietary C-SPC + ISF tended to increase plasma superoxide dismutase activity on days 28 (P = 0.085) and 42 (P = 0.075) and reduce plasma malondialdehyde (MDA) content on day 42 (P = 0.089), as well as significantly decreased jejunal mucosa MDA content on day 42 (P < 0.05). However, no significant difference in the expression of tight junction genes among the three groups was found (P > 0.05). In conclusion, our results suggest that a long-term exposure to soybean isoflavones enhances the growth performance, protects the intestinal morphology and improves the antioxidative properties in pigs.     

Close interactions between lncRNAs,lipid metabolism and ferroptosis in cancer

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabolism and ferroptosis in cancer. In this review, we mainly summarized the mechanism by which lncRNAs regulate aberrant lipid metabolism in cancer, illustrated that lipid metabolism can also influence the expression of lncRNAs, and discussed the mechanism by which lncRNAs affect ferroptosis. A comprehensive understanding of the interactions between lncRNAs, lipid metabolism and ferroptosis could help us to develop novel strategies for precise cancer treatment in the future.     

Effects of alpha-tocopherol on an animal model of tauopathies

We have reported that transgenic (Tg) mice overexpressing human tau protein develop filamentous tau aggregates in the CNS. We overexpressed the smallest human tau isoform (T44) in the mouse CNS to model tauopathies. These tau Tg mice acquire age-dependent CNS pathologies, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Therefore, these Tg mice are a model that can be exploited for drug discovery in studies that target amelioration of tau-induced neurodegeneration as well as for elucidating mechanisms of tau pathology in various neurodegenerative tauopathies. Oxidative stress has been implicated in the pathogenesis of various neurodegenerative diseases, including tauopathies, and many epidemiological, clinical, and basic studies have suggested the neuroprotective effects of vitamin E in neurodegenerative diseases. To elucidate the role of oxidative damage in the pathological mechanisms of these Tg mice, we fed them alpha-tocopherol, the major component of antioxidant vitamin E. Supplementation of alpha-tocopherol suppressed and/or delayed the development of tau pathology, which correlated with improvement in the health and attenuation of motor weakness in the Tg mice. These results suggest that oxidative damage is involved in the pathological mechanisms of the tau Tg mice and that treatment with antioxidative agents like alpha-tocopherol may prevent neurodegenerative tauopathies.     

荷叶水提物对实验性肥胖大鼠脂代谢的影响及机制

目的：探讨荷叶水提物的减肥降脂作用及机制。方法：通过离体脂肪组织灌流实验观察荷叶水提物对正常SD大鼠离体脂肪组织游离脂肪酸（FFA）释放的影响;利用高糖高脂饮食诱导建立实验性肥胖大鼠模型,探讨荷叶水提物给药4周后,大鼠体重和血脂水平的变化,并采用RT-PCR和免疫组化技术对脂肪组织过氧化物酶体增殖物激活受体γ（PPAR-γ）和瘦素（leptin）表达进行检测。结果：离体实验发现荷叶水提物可明显促进离体脂肪组织FFA的释放。在体实验发现中剂量荷叶（60 mg/kg）与奥利斯他相似,可使实验性肥胖大鼠体重、血脂水平明显下降（P<0.05）,使脂肪组织PPAR-γ和瘦素的表达明显下降（P<0.05）。结论：荷叶水提物可通过改善大鼠脂肪组织PPAR-γ和leptin的表达,促进脂肪的动员和分解,降低肥胖大鼠体重和血脂水平,有望研发为减肥药物。     

2株动物微生态制剂菌的分离鉴定及其生物学特性初步研究

目的从饲料中进行微生物的分离与培养,筛选动物微生态制剂候选菌株。方法利用变性梯度凝胶电泳(DGGE)筛选得到的7株微生物区分为2种菌,经测序确定其为热带假丝酵母和植物乳杆菌;检测了不同pH、温度、胆盐、金属铜和需/厌氧对其生长的影响。结果当pH小于2.5或铜离子高于150 ppm时,植物乳杆菌无法生长,而热带假丝酵母数量略有下降;胆盐和金属离子对2种菌影响较小,42℃培养条件下相对于30℃培养时热带假丝酵母数量下降了6个数量级。结论筛选得到的2株菌具有应用于动物微生态制剂的潜力,为动物微生态制剂候选菌筛选和评价提供了基础数据。     

Effects of consumption of probiotics and prebiotics on serum lipid levels in humans

The objective of this article is to review existing studies concerning the effects of probiotics and prebiotics on serum cholesterol concentrations, with particular attention on the possible mechanisms of their action. Although not without exception, results from animal and human studies suggest a moderate cholesterol-lowering action of dairy products fermented with appropriate strain(s) of lactic acid bacteria and bifidobacteria. Mechanistically, probiotic bacteria ferment food-derived indigestible carbohydrates to produce short-chain fatty acids in the gut, which can then cause a decrease in the systemic levels of blood lipids by inhibiting hepatic cholesterol synthesis and/or redistributing cholesterol from plasma to the liver. Furthermore, some bacteria may interfere with cholesterol absorption from the gut by deconjugating bile salts and therefore affecting the metabolism of cholesterol, or by directly assimilating cholesterol. For prebiotic substances, the majority of studies have been done with the fructooligosaccharides inulin and oligofructose, and although convincing lipid-lowering effects have been observed in animals, high dose levels had to be used. Reports in humans are few in number. In studies conducted in normal-lipidemic subjects, two reported no effect of inulin or oligofructose on serum lipids, whereas two others reported a significant reduction in serum triglycerides (19 and 27%, respectively) with more modest changes in serum total and LDL cholesterol. At present, data suggest that in hyperlipidemic subjects, any effects that do occur result primarily in reductions in cholesterol, whereas in normal lipidemic subjects, effects on serum triglycerides are the dominant feature.     

大豆异黄酮对去卵巢大鼠骨密度及骨代谢影响的实验研究

目的 探讨大豆异黄酮对去卵巢大鼠骨丢失的防治作用及其作用机理。方法 选用卵巢切除大鼠所诱发的骨质疏松模型,给与大豆异黄酮治疗。三个月后测定大鼠骨密度及骨代谢相关生化指标。结果 大豆异黄酮可提高卵巢切除大鼠的骨密度及血清雌激素水平,降低尿钙（Ca),尿磷（P）及尿羟脯氨酸（HOP）的排泄,同时降低血清总碱性磷酸酶（ALP）,骨碱性磷酸酶（BALP）,及抗酒石酸酸性磷酸酶（TRACP）的活性,还可使血清骨钙素（BGP）的浓度降低,促使卵巢切除大鼠子宫的相对重量增加,其作用与剂量相关。结论 小剂量大豆异黄酮有类似雌激素样作用,可有效防治卵巢切除大鼠的骨量丢失,其作用机制可能是通过降低骨转换率实现的。