Ovarian hypercytolipidemia induced by obese (ob/ob) and diabetes (db/db) mutations: basis of female reproductive tract involution II

The diabetes (db/db) and obese (ob/ob) genotype mutations induce a progressive, hypercytolipidemic condition within the ovarian compartments of the female reproductive tract that results in sterility and premature organ involution in C57BL/KsJ mice. The current studies focus on the ultrastructural changes that occur within the ovarian interstitial, thecal, and follicular granulosa cell layers during the progressive expression of these mutations which promote tissue cytolipidemia-induced organoinvolution. Control (normal: +/?), diabetes (db/db), and obese (ob/ob) genotype groups were prepared for high resolution light (HRLM) and transmission electron microscopic (TEM) analysis of ovarian tissue samples collected from 4 (young)- to 20 (aged)-week-old mice, allowing for the progressive influences of the mutational aberrations on tissue structure to be evaluated. Compared to controls, both (ob/ob) and (db/db) mutations induced a dramatic increase in ovarian interstitial, thecal and follicular granulosa cytolipid vacuole accumulations, which increased in density between 4 and 20 weeks of age. Initially, lipid vacuoles aggregated in the interstitial and thecal regions of ovarian follicles in response to the hyperglycemic-hypertriglyceridemic metabolic conditions typical of both (ob/ob) and (db/db) groups. Progressive cytoplasmic movement of the lipid pools established a perinuclear isolation from associated cytoplasmic organelles. Progressive lipid accumulations forced cytoplasmic organelles to peripheral cell compartments and altered the follicular cell profile towards that of adipocyte-like entities relative to controls. The progressive hypercytolipidemia-induced alterations in cell structure disrupted normal tissue continuity, which culminated in premature ovarian organo-involution and female reproductive sterility.     

达格列净联合利拉鲁肽对肥胖型T2DM患者的血糖控制、胰岛素功能的影响及安全性分析

摘要 目的：探究达格列净联合利拉鲁肽对肥胖型2型糖尿病（T2DM）患者的血糖控制、胰岛素功能的影响及安全性分析。方法：将106例肥胖型T2DM患者按照治疗方法分为两组：联合组患者采用达格列净联合利拉鲁肽治疗（55例）、对照组采用利拉鲁肽治疗（51例）。记录对比两组治疗疗效、不良反应发生情况。检测两组治疗前后血脂代谢指标[脂联素(APN)、总胆固醇（TC）、甘油三酯（TG)]、胰岛素功能指标[稳态胰岛 β 细胞分泌功能指数（HOMA-β）、胰岛素评价指数（HOMA-IR）]、血压[收缩压（SBP）、舒张压（DBP）]以及身体质量指数（BMI）变化。结果：联合组治疗总有效率高于对照组（P＜0.05）,不良反应总发生率高于对照组（P＜0.05）。治疗后,观察组外周血TC、TG水平、HOMA-IR以及SBP、DBP低于对照组（P＜0.05）,APN浓度、HOMA-IR以及BMI高于对照组（P＜0.05）。结论：达格列净联合利拉鲁肽可有效控制肥胖型T2DM患者的血糖、血脂以及血压水平,保护胰岛功能,但也可能导致更多的不良反应。     

黄连素对肥胖小鼠肠道菌群的影响及其机制

为了探索黄连素对肥胖小鼠肠道菌群的影响和作用机制,本研究将40只雄性昆明种小鼠随机分为空白组、模型组、黄连素高剂量组、黄连素中剂量组和黄连素低剂量组,每组8只,除空白组外,其余4组给予高脂饮食,建立实验性肥胖小鼠模型。造模14 d后,全部给予正常饮食,黄连素高、中、低剂量组灌胃给予每天0.1～0.3 mL/10 g的药物干预,空白组和模型组给予等剂量的生理盐水,给药持续14 d。每周称量两次体质量,并分别于实验第0、14、28天从眼眶取血测定血脂和炎性因子的含量,收集小鼠粪便测定乳酸杆菌和双歧杆菌的数量。研究结果表明:空白组和模型组小鼠的体质量在第14天时有明显差异,造模成功;实验第28天,黄连素各给药组小鼠的体质量与模型组相比有显著性差异。模型组双歧杆菌、乳酸菌的数量和血脂水平与空白组比较有显著性差异,黄连素给药组能显著改善肥胖小鼠的血脂水平和双歧杆菌、乳酸杆菌的数量。本研究结果初步得出结论认为:黄连素改善肥胖小鼠的作用机制可能与脂质代谢、炎性反应和肠道微环境的改变密切相关。     

The effects of treadmill exercise on expression of UCP-2 of brown adipose tissue and TNF-α of soleus muscle in obese Zucker rats

Sorts of abnormal state, obesity and inflammation are involved in a number of serious disease occurring and both of them became important research topics among molecular biologists. UCP-2 and TNF-α respectively reflecting obese and inflammatory status have often been used to evaluate the effects of independent variable, such as exercise, on them. Because exercise has shown its potent control on obesity and inflammation, it is necessary to determine if exercise is working via same bioindices. The purpose of this study was to determine the effects of different treadmill exercise intensities on UCP-2 of brown adipose tissue and TNF-α of soleus muscle during 8 weeks in Zucker rat. Zucker rats were divided into four groups (n = 7 in each group): control group, low intensity exercise group, moderate intensity exercise group and high intensity exercise group. Zucker rats of the exercise groups were made to run on a motorized treadmill for 30 minutes once a day during 8 weeks. Rats were sacrificed 24 hours after the last bout of exercise. Blood glucose in Zucker rats were measured by Gluco-Card Ⅱ. Brown adipose tissue were extracted to analyze the level of UCP-2 and TNF-α, respectively. UCP-2 and TNF-α were analyzed using the Western Blotting technique. Statistical techniques for data analysis were repeated measure ANOVA and one way ANOVA to determine the difference between groups, and for post hoc test was Duncan'' test. The 5% level of significance was utilized as the critical level for acceptance of hypotheses for the study. The following results were obtained from this study; UCP-2 protein expression of brown adipose tissue in Zucker rats were increased significantly following exercise of the low and moderate intensities compared to those of control group after 8 weeks. It was shown that TNF-α protein expression of soleus muscle in Zucker rats were decreased significantly following exercise of the low and moderate intensities compared to those of control group after 8 weeks. But no significant differences in levels of fasting glucose were shown between groups. The present data suggested that low and moderate intensities treadmill exercise may improve glycometabolism control and fat oxidation by up-regulating UCP-2 expression. In addition, we found low and moderate intensities reduce damages on skeletal muscle by down-regulation the TNF-α in Zucker rats. Thus, the low and moderate intensity exercise are appropriate for anti-obesity and inflammatory effects.     

加味补中益气汤治疗肥胖型多囊卵巢综合征患者的疗效及对子宫内膜容受性和糖脂代谢的影响

摘要 目的：探讨加味补中益气汤治疗肥胖型多囊卵巢综合征（PCOS）患者的疗效及对子宫内膜容受性和糖脂代谢的影响。方法：选择2018年3月~2020年5月期间我院收治的肥胖型PCOS患者280例，采用抽签法分为观察组140例和对照组140例。对照组给予二甲双胍片治疗，观察组给予加味补中益气汤治疗，对比两组疗效、体质量指数（BMI）、腰臀比、性激素指标[雌二醇（E2），促黄体生成激素（LH）、卵泡刺激素（FSH）]、子宫内膜容受性指标[子宫内膜厚度、子宫内膜螺旋动脉搏动指数（PI）与阻力指数（RI）]、糖脂代谢指标[总胆固醇(TC)、低密度脂蛋白 (LDL-C)、甘油三酯(TG)、高密度脂蛋白 (HDL-C)、空腹血糖（FPG）]。结果：观察组的临床总有效率为92.14%（129/140），高于对照组的80.71%（113/140）（P<0.05）。治疗3个月经周期后，两组BMI、腰臀比、PI、RI、LH、FSH、TC、LDL-C、TG、FPG均下降，且观察组低于对照组（P<0.05）。治疗3个月经周期后，两组子宫内膜厚度、HDL-C、E2升高，且观察组高于对照组（P<0.05）。结论：加味补中益气汤治疗肥胖型PCOS患者，可降低患者体质量，调节性激素、子宫内膜容受性和糖脂代谢水平，具有较好的疗效。     

不同体位对肥胖产妇椎间隙定位的影响

目的:探讨体位对肥胖产妇椎间隙定位准确性的影响。方法:选择2018年1月-6月在上海市同仁医院建卡并定期产检且预产期在此期间的209例肥胖产妇,根据不同穿刺体位按随机数字表法将其分为坐位组(n=104)和侧卧位组(n=105),采用超声检测作为金标准进行椎间隙定位,比较不同体位下触诊定位椎间隙的精准性,及肥胖程度与定位准确性的关系。结果:与侧卧位组比较,坐位组L3-4椎间隙定位时间显著缩短,皮肤至腰椎棘突距离、红色(手法定位)与黑色标记(超声定位)距离明显缩小(P0.05)。与侧卧位组比较,坐位组一次穿刺成功率明显升高,穿刺时间明显缩短(P0.05)。随着BMI的增加,椎间隙定位时间显著延长,皮肤至腰椎棘突距离、红色与黑色标记距离、节段误差率明显增加(P0.05)。结论:肥胖产妇椎间隙定位准确性与体位及肥胖程度密切相关,坐位下椎间隙触诊定位的准确性优于侧卧位。     

二甲双胍对多囊卵巢综合征肥胖型患者LH 和FSH 的影响

目的:探讨二甲双胍对多囊卵巢综合征肥胖型患者血清中胰岛素、LH和FSH水平的影响。方法:将84例PCOS肥胖型患者随机分成44例对照组(克罗米芬)和40例观察组(二甲双胍),采用放射免疫法测定黄体生成素(LH)和卵泡刺激素(FSH)的水平,分别于服药前(0分钟)和服后60、120分钟经前臂静脉采血,测血糖浓度及血清胰岛素水平。结果:对照组患者治疗前0min、60min及120min的血糖OGTT分别为(4.57±0.25)mmol/L、(8.38±7.05)mmol/L及(7.21±0.12)mmol/L,治疗后0min、60min及120min的血糖OGTT无明显变化。观察组患者治疗前0min、60min及120min的血糖OGTT分别为(4.11±0.31)mmol/L、(8.23±6.57)mmol/L及(7.25±0.13)mmol/L,治疗后0min、60min及120min的血糖OGTT明显降低。对照组患者治疗前血清中胰岛素为(47.32±9.52)U/m l,治疗后为(42.25±7.65)U/ml,治疗前后无明显差异。观察组患者治疗前血清中胰岛素为(46.41±6.11)U/ml,治疗后血清胰岛素水平明显降低。对照组患者治疗后血清中LH为(17.22±2.14)mU/ml,FSH为(1.24±0.33)mU/m l,而与对照组相比,观察组患者血清中的LH明显降低,而FSH水平升高。结论:二甲双胍导致多囊卵巢综合征患者血清中胰岛素水平降低,从而减轻了胰岛素对LH的刺激作用,使LH水平下降,FSH升高,进而改善机体的激素紊乱,最终达到治疗PCOS的目的。     

Vascular endothelial cells and smooth muscle cells mediate carbachol-induced hepatocyte proliferation via muscarinic receptors and IP3/PKC signaling cascades

An acetylcholine (ACh) agonist, carbachol (Cch), causes hepatocytes to proliferate in the presence of hepatic nonparenchymal cells (HNPCs). To identify the HNPCs and ACh receptor subtypes involved in carbachol-induced hepatocyte proliferation (CIHP), we examined two types of vascular cells as candidates for HNPCs mediating CIHP in cocultures of hepatocytes using the Transwell filter insert. In the coculture with vascular smooth muscle cells (VSMCs) or endothelial cells (VECs), but not in the monoculture, 72 h treatment with Cch significantly increased the numbers of hepatocytes. The results suggest that both VSMCs and VECs are involved in CIHP through soluble factors secreted from these cells. Interestingly, coculture with VECs, but not with VSMCs, markedly increased the number of hepatocytes, even in the absence of Cch. Cell proliferation assays using an analogue of thymidine, bromodeoxyuridine (BrdU), demonstrated that the hepatocytes in both cocultures transiently replicated their chromosomes 12 h after Cch administration. Blocking the muscarinic type 1 ACh receptor (M₁), M_3/5, intracellular inositol triphosphate (IP₃) receptor, or protein kinase C (PKC) pathways inhibited VSMC-mediated CIHP, whereas blocking the M_3/5, IP₃ receptor, or PKC pathways inhibited VEC-mediated CIHP. Co-culturing hepatocytes with both types of vascular cells markedly increased their albumin content, but addition of Cch had no effect. In conclusion, VSMCs among vascular cells mediate CIHP through M₁, M_3/5, and IP₃/PKC signal transduction pathways, whereas VECs do so through M_3/5, and IP₃/PKC pathways.     

Similar incretin secretion in obese and non-obese Japanese subjects with type 2 diabetes

Incretin secretion and effect on insulin secretion are not fully understood in patients with type 2 diabetes. We investigated incretin and insulin secretion after meal intake in obese and non-obese Japanese patients with type 2 diabetes compared to non-diabetic subjects. Nine patients with type 2 diabetes and 5 non-diabetic subjects were recruited for this study. Five diabetic patients were obese (BMI ? 25) and 4 patients were non-obese (BMI < 25). In response to a mixed meal test, the levels of immunoreactive insulin during 15-90 min and C-peptide during 0-180 min in non-obese patients were significantly lower than those in obese patients. Total GLP-1 and active GIP levels showed no significant difference between obese and non-obese patients throughout the meal tolerance test. In addition, there were no significant differences between diabetic patients and non-diabetic subjects. In conclusion, incretin secretion does not differ between Japanese obese and non-obese patients with type 2 diabetes and non-diabetic subjects.     

Omental and subcutaneous adipose tissue steroid levels in obese men

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.