Time course of liver lipid infiltration in ovariectomized rats: impact of a high-fat diet

OBJECTIVES: The present study was undertaken to determine the time course of liver lipid infiltration in ovariectomized (Ovx) rats and the impact of high-fat (HF; 42% kJ) feeding on this response. METHODS: In a first step, Ovx rats were compared to Sham-operated (Sham) and Ovx rats supplemented with 17beta-estradiol (OvxE2) to evaluate the effect of estrogen removal. In a second time, Ovx rats fed a HF diet (OvxHf) were compared with normally fed Ovx rats. Animals were killed after 3, 8, and 13 weeks of their respective treatment (n=8 rats/group). We measured liver triacylglycerol (TAG) content, fat pad mass, and several other plasma parameters. RESULTS: Ovariectomy resulted in the typical increase in energy intake and body weight. Liver TAG accumulation was 35, 43, and 99% higher in Ovx than in Sham rats after 3, 8, and 13 weeks, respectively. The ovariectomy-induced liver lipid infiltration was completely prevented by estrogen replacement. On the opposite, plasma TAG concentrations were lower in Ovx than in Sham and OvxE2 rats. HF feeding in Ovx rats resulted in a significant (P<0.05; 38 versus 22 mg/g at 13-week) accumulation of fat in liver as compared to normally fed Ovx rats. CONCLUSIONS: Ovariectomy results in a progressive accumulation of fat in liver over a 13-week period. In addition, HF feeding in Ovx rats lead to an even more severe liver lipid infiltration. These data indicate that the absence of estrogens in rat favours fat accretion in liver, which is highly amplified by a HF diet.     

氧化应激在高脂高盐饮食伴高糖饮水诱导的代谢综合征肾病大鼠中的作用

目的: 构建饮食诱导的代谢综合征(MS)肾病大鼠模型,并探讨氧化应激在肾脏损伤中的作用。方法: 7周龄雄性SD大鼠随机分为正常对照组(n=10)和MS模型组(n=10)。MS大鼠喂饲高脂高盐(HFS)饲料和20%蔗糖饮水20周。测定尾动脉收缩压(SBP);测空腹血糖(FBG)、血脂和胰岛素(FIns)水平,计算稳态胰岛素评价指数(HOMA-IR);测肌酐、尿蛋白、尿白蛋白和尿钠含量,并计算肌酐清除率(Ccr)、蛋白排泄率(UPE)、白蛋白排泄率(UAE)和钠排泄率(USE);测肾脏组织总抗氧化能力(T-AOC)、抑制超氧阴离子能力(ISAC)、丙二醛(MDA)含量以及抗氧化酶活性;Western blotting检测肾脏铜锌超氧化物歧化酶(Cu/Zn-SOD) 和NADPH氧化酶亚单位p47^phox、p22^phox蛋白表达;PAS和Masson染色观察肾脏病理变化并进行评分。结果: 与正常组相比,MS大鼠SBP、血脂、FIns、HOMA-IR、USE和UAE增高;肾脏T-AOC、ISAC和SOD活性降低,MDA含量增加;p47^phox蛋白表达增高,Cu/Zn-SOD蛋白表达降低;肾小球硬化评分升高。结论: 喂饲大鼠HFS饮食和高糖饮水可建立模拟大部分临床特征的MS肾病模型。NADPH氧化酶表达增高和SOD表达减少而引起的氧化应激是导致MS大鼠肾脏损伤的机制之一。     

芝麻素对高脂、高糖饲养大鼠血脂血糖及血管重构的影响

目的：探讨芝麻素对高脂、高糖饲养大鼠血脂血糖及血管重构的影响。方法：大鼠高脂高糖饮食24周，于第9周开始连续口服芝麻素(120、60、30 mg·kg^-1·d^-1)16周。测血糖、血脂、血压、血清与血管总抗氧化能力和过氧化氢含量。主动脉HE染色和Masson染色分别观察主动脉组织学和胶原纤维变化。肠系膜动脉HE染色，病理图像分析系统测定血管中膜厚度(media thickness，M)、血管内径(luminal radius，L)和中膜厚度与内径比值（M/L）。免疫组化法观察主动脉诱导型一氧化氮合酶蛋白表达。结果：与模型组相比，芝麻素高中剂量组血糖、血脂和血压明显下降（P<0.01）；总抗氧化能力显著提高，过氧化氢含量明显降低（P<0.01或P<0.05）；主动脉iNOS蛋白表达和胶原纤维沉积明显减少；血管内膜和平滑肌细胞增殖减轻；系膜动脉血管M与M/L明显减少，L明显增加(P<0.01)。结论：芝麻素能纠正高脂、高糖诱导大鼠糖脂代谢异常,并抑制血压升高、改善血管重构。     

限食对高脂喂养大鼠肝脏内质网应激的影响

目的：观察限食对高脂喂养大鼠肝脏内质网应激标志伴侣蛋白78 kD糖调节蛋白（GRP78）mRNA表达的影响，以进一步了解饮食控制对肥胖及胰岛素抵抗影响的机制。方法：雄性Wistar大鼠24只，随机分为正常对照组（NC）、高脂饮食组（HF）、热卡限制组（CR），每组8只。NC组和HF组分别给予普通饲料（脂肪热卡比18.94%）和高脂饲料（脂肪热卡比50.55%）喂养12周，自由进食。CR组给予自由高脂饲料8周后，改为半量正常饲料（半量为同龄对照组自由进食量的一半）继续喂养4周。造模结束后检测动物胰岛素抵抗指数（HOMAIR）、内脏脂肪重量/体重比值和血清生化指标变化，光镜和电镜下观察大鼠肝脏组织学改变，RT-PCR半定量检测大鼠肝脏GRP78 mRNA的表达。结果：（1）HF组空腹血胰岛素(FIns) (27.51±3.51) mU/L vs (15.46±2.25) mU/L、甘油三酯（TG）(1.35±0.25) mmol/L vs (0.67±0.10) mmol/L、胆固醇（TC）(2.59±0.34) mmol/L vs (1.41±0.28) mmol/L及胰岛素抵抗指数HOMAIR(5.85±0.23) vs (2.85±0.60)较NC组明显升高(P＜0.01)，且肝脏中脂质沉积明显。（2）限食4周后，CR组的Fins(11.25±2.42) mU/L vs (27.51±3.51) mU/L、TG(0.45±0.06) mmol/L vs (1.35±0.25) mmol/L、TC(1.06±0.15) mmol/L vs (2.59±0.34) mmol/L和HOMAIR(1.91±0.38) vs (5.85±0.23)明显低于HF组(P＜0.01)，同时肝脏中脂质沉积也减轻。（3）电镜下，HF组内质网肿胀断裂，核糖体脱落，糖原溶解，CR组则基本恢复正常。（4）HF组大鼠肝脏中GRP78 mRNA表达明显高于NC组（29.36±3.54 vs 16.51±1.73），而CR组则明显低于HF组（13.70±2.35 vs 29.36±3.54）。结论：合理限制饮食能有效减轻高脂喂养所致的脂质代谢紊乱和胰岛素抵抗，其作用机制至少与肝脏组织中的内质网应激相关蛋白GRP78的mRNA表达受抑有关。     

Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community,China

Our objective was to examine associations of adult weight gain and nonalcoholicfatty liver disease (NAFLD). Cross-sectional interview data from 844 residentsin Wan Song Community from October 2009 to April 2010 were analyzed inmultivariate logistic regression models to examine odds ratios (OR) and 95%confidence intervals (CI) between NAFLD and weight change from age 20.Questionnaires, physical examinations, laboratory examinations, andultrasonographic examination of the liver were carried out. Maximum rate ofweight gain, body mass index, waist circumference, waist-to-hip ratio, systolicblood pressure, diastolic blood pressure, fasting blood glucose, cholesterol,triglycerides, uric acid, and alanine transaminase were higher in the NAFLDgroup than in the control group. HDL-C in the NAFLD group was lower than in thecontrol group. As weight gain increased (measured as the difference betweencurrent weight and weight at age 20 years), the OR of NAFLD increased inmultivariate models. NAFLD OR rose with increasing weight gain as follows: OR(95%CI) for NAFLD associated with weight gain of 20+ kg compared to stableweight (change <5 kg) was 4.23 (2.49-7.09). Significantly increased NAFLD ORwere observed even for weight gains of 5-9.9 kg. For the “age 20 to highestlifetime weight” metric, the OR of NAFLD also increased as weight gainincreased. For the “age 20 to highest lifetime weight” metric and the “age 20 tocurrent weight” metric, insulin resistance index (HOMA-IR) increased as weightgain increased (P<0.001). In a stepwise multivariate regression analysis,significant association was observed between adult weight gain and NAFLD(OR=1.027, 95%CI=1.002-1.055, P=0.025). We conclude that adult weight gain isstrongly associated with NAFLD.     

Coping style predicts the (in)sensitivity for developing hyperinsulinemia on a high fat diet in rats

The aim of this study was to explore interactions between coping style and diet as risk factors for developing insulin resistance in rats. We hypothesized that rats characterized by a passive coping strategy are more susceptible for developing insulin resistance and visceral obesity than proactively coping rats, particularly on a high (45%) fat diet. This hypothesis was tested by comparing 1) insulin and glucose responses to an intravenous glucose tolerance test (IVGTT), and 2) body fat distribution, in two rat models for passive and proactive coping styles. We found that the most extremely passive rats are characterized by elevated insulin levels during a IVGTT, even on chow. Moderately passive rats display normal insulin responses under chow conditions, but develop insulin resistance on a high fat diet. Proactive rats are remarkably resistant to insulin resistance and visceral obesity, even when overfeeding on a high fat diet. Carcass analysis revealed that passive rats are characterized by increased epididymal fat deposition, which is in line with the observed differences in insulin resistance. We conclude that a passive personality is prone to develop insulin resistance and visceral obesity on a palatable fat diet and a proactive personality might be protected against the development of diet-induced insulin resistance.     

微粒化非诺贝特对高脂饲养SHR脂毒性及胰岛素敏感性的影响

目的：观察微粒化非诺贝特对高脂饲养自发性高血压大鼠(SHR) 脂毒性及胰岛素敏感性（IS）的影响。方法:将27只SHR随机分为3组，1组给予标准饲料，其余2组分别给予高脂饲料、高脂饲料+非诺贝特100 mg·kg-1·d-1灌胃。3个月后，观察比目鱼肌细胞内脂滴沉积情况，计算脂质沉积指数（LAI）；进行葡萄糖耐量试验及游离脂肪酸测定。结果:(1) 与标准饲料组比较，高脂饲料组SHR体重和血浆甘油三酯（TG）、胆固醇（TC）水平明显增高，高密度脂蛋白胆固醇（HDL-C）水平明显降低(P＜0.05)，而非诺贝特治疗组与标准饲料组比较血压明显下降，HDL-C明显升高，体重、TG及TC水平无明显差异。(2) 高脂饲料组空腹血糖、游离脂肪酸、葡萄糖曲线下面积明显高于标准饲料组，胰岛素敏感指数显著低于标准饲料组（0.0038±0.0007 vs 0.0053±0.0013, P＜0.05）。非诺贝特组各项指标与标准饲料组无明显差异（P＞0.05）。(3)与标准饲料组相比，高脂饲料组比目鱼肌细胞内有大量脂质沉积（LAI: 6.42±0.59 vs 1.98±0.97, P＜0.05），非诺贝特治疗组比目鱼肌细胞内脂质含量显著减少，与标准饲料组无明显差别（LAI: 3.32±0.77 vs 1.98±0.97, P＞0.05）。经协方差分析排除血糖、血压因素影响后，上述差别仍有意义（F=10.46, P＜0.05）。（4） 骨骼肌脂质沉积指数与胰岛素敏感指数呈负相关（r=-0.58, P＜0.05），与TG、FFA、体重、葡萄糖曲线下面积呈正相关。结论:非诺贝特除了调脂外，还具有降低高脂饲养SHR体重、血压、脂毒性和改善胰岛素敏感性多重效应。     

MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats

Monosodium l-glutamate (MSG), an umami taste substance, may be a key molecule coupled to a food intake signaling pathway, possibly mediated through a specific l-glutamate (GLU) sensing mechanism in the gastrointestinal tract. Here we investigated the effect of the spontaneous ingestion of a 1% MSG solution and water on food intake and body weight in male Sprague-Dawley rats fed diets of varying caloric density, fat and carbohydrate contents. Fat mass and lean mass in the abdomen, blood pressure, and several blood metabolic markers were also measured. Rats given free access to MSG and water showed a high preference (93-97%) for the MSG solution, regardless of the diet they consumed. Rats ingesting MSG had a significantly smaller weight gain, reduced abdominal fat mass, and lower plasma leptin levels, compared to rats ingesting water alone. Naso-anal length, lean mass, food and energy intakes, blood pressure, blood glucose, and plasma levels of insulin, triglyceride, total cholesterol, albumin, and GLU were not influenced by the ingestion of the MSG solution. These same effects were observed in a study of adult rats. Together, these results suggest that MSG ingestion reduces weight gain, body fat mass, and plasma leptin levels. Moreover, these changes are likely to be mediated by increased energy expenditure, not reduced energy intake or delayed development. Conceivably, these effects of MSG might be mediated via gut GLU receptors functionally linked to afferent branches of the vagus nerve in the gut, or the afferent sensory nerves in the oral cavity.     

Comparison of metabolic profile and abdominal fat distribution between karyotypically normal women with premature ovarian insufficiency and age matched controls

Objective

We designed a prospective case-control study in order to investigate the lipid profiles, insulin sensitivity, presence of metabolic syndrome (MetS) and the abdominal fat distribution in karyotypically normal women with premature ovarian insufficiency (POI).

Methods

Anthropometric measurements, FSH, estradiol, total testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI), fasting glucose and insulin, homeostatic model for insulin resistance (HOMA-IR), lipid profile, the prevalence of MetS and ultrasonographic abdominal fat measurements were assessed in 56 women with POI and 59 healthy controls at the same age range.

Results

Serum levels of T, SHBG and FAI were not significantly different between both groups. Total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were higher in women with POI. There were no differences in glucose, insulin, HOMA-IR, low-density lipoprotein cholesterol (LDL-C), triglyceride levels between the two groups. A significant positive correlation was identified between T and TG and also between FAI and LDL-C; SHBG levels were correlated inversely with FSH, and positively with HDL-C in women with POI. The presence of MetS was significantly higher in women with POI. The subcutaneous, preperitoneal and visceral fat thicknesses were not significantly different between the groups.

Conclusions

Early cessation of ovulatory function may associated with higher levels of serum TC and HDL-C, but does not seem to cause differences in abdominal fat distribution in women with POI. POI is associated with higher risk of MetS.     

Effect of the detraining status on high-fat diet induced fat accumulation in the adipose tissue and liver in female rats

The purpose of the present study was to investigate the effects of a high-fat diet (HFD) in previously trained rats that have been detrained for different periods. Two groups of female rats were, first, either treadmill trained for 8 weeks or remained sedentary (Sed). Trained animals, thereafter, remained inactive for 4 weeks (Inact-4 weeks), while fed a standard diet, before being submitted to a high-fat diet (42% kcal of fat) for an additional 2 or 6 weeks. The order was reversed in a 3rd group in which rats were first kept sedentary for 4 weeks before being submitted to the same 8-week training program that ended with the initiation of the HFD (Inact-0 week). Fat accumulation in the mesenteric depot (P<0.05) and in the sum of 3 intra-abdominal (urogenital, retroperitoneal, and mesenteric; P=0.065) tissues in response to the HF feeding was higher in trained rats kept inactive for 4 weeks than in Sed and Inact-0 week animals. Liver triacylglycerol accumulation also showed a tendency to be higher (P<0.07) in Inact-4 weeks than in Inact-0 week rats. These changes were not associated with significant changes in fat cell diameter and number in the mesenteric adipose tissue. When rats in all groups were subdivided into obesity prone (OP) and obesity resistant (OR) on the basis of the change in body weight gain in response to the HFD, liver lipid infiltration was higher (P<0.01) in OP Inact-4 weeks rats than in all other groups. The present results indicate that previously trained rats that have been inactive for a while maintain higher body adiposity in response to a HFD than in freshly inactive and sedentary rats.     

Paraventricular nucleus lesions in weanling female rats result in normophagia, normal body weight and composition, linear growth and normal levels of several plasma substrates

Female weanling rats received small (1 mAmp for 5 sec) electrolytic lesions in the paraventricular nuclei. Sham-operated rats served as controls. The rats were maintained for 42 days and body weight, linear growth, Lee Index, food intake and efficiency of food utilization were determined throughout the study. Plasma glucose, glycerol, free fatty acids, total protein and carcass fat and protein were determined at sacrifice. There was no significant difference between the lesioned and the sham-operated rats in any of the parameters measured. The findings are interpreted to mean that the PVN of the weanling rat is not functionally mature or alternatively, that there exists a sex difference in weanling rats in response to PVN lesions.     

Effect of high-fat diet on metabolic indices,cognition, and neuronal physiology in aging F344 rats

The prevalence of obesity and type 2 diabetes increases with age. Despite this, few studies have examined these conditions simultaneously in aged animals, and fewer studies have measured the impact of these conditions on brain function. Using an established animal model of brain aging (F344 rats), we investigated whether a high-fat diet (HFD) exacerbates cognitive decline and the hippocampal calcium-dependent afterhyperpolarization (a marker of age-dependent calcium dysregulation). Young and mid-aged animals were maintained on control or HFD for 4.5 months, and peripheral metabolic variables, cognitive function, and electrophysiological responses to insulin in the hippocampus were measured. HFD increased lipid accumulation in the periphery, although overt diabetes did not develop, nor were spatial learning and memory altered. Hippocampal adiponectin levels were reduced in aging animals but were unaffected by HFD. For the first time, however, we show that the AHP is sensitive to insulin, and that this sensitivity is reduced by HFD. Interestingly, although peripheral glucose regulation was relatively insensitive to HFD, the brain appeared to show greater sensitivity to HFD in F344 rats.     

GLP-1对非酒精性脂肪肝病大鼠胰岛素抵抗及PKCε的影响

 目的: 探讨胰高血糖素样肽1(GLP-1)对非酒精性脂肪肝病SD大鼠的治疗作用及可能的机制。方法: 32只SPF级雄性SD大鼠(体重约130 g)随机抽取21只予高脂饮食(88%普通饲料+10%猪油+2%胆固醇),余下11只予普通饲料饮食作为空白对照组;12周后,将高脂饮食大鼠随机分为2组,每组10只:高脂组予高脂饮食并腹腔注射等体积的无菌生理盐水,治疗组予高脂饮食并腹腔注射利拉鲁肽(GLP-1类似物)注射液(0.6 mg·kg^-1·d^-1)。治疗4周后处死全部大鼠抽取静脉血并取肝脏组织。全自动生化仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)及葡萄糖(GLU)含量;ELISA法测定血清胰岛素含量。石蜡包埋肝组织做病理切片及HE染色;real-time PCR法测定肝组织蛋白激酶Cε(PKCε)mRNA的表达,Western blot 测定肝组织胞浆PKCε蛋白表达。结果: 与正常对照组相比,高脂组的ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均明显升高;GLP-1治疗组与高脂组相比ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均下降,差异有统计学意义(P<0.05); real-time PCR及Western blot结果提示高脂组PKCε mRNA及蛋白表达减少 (P<0.05);GLP-1治疗组PKCε mRNA及蛋白表达增多(P<0.05)。结论: GLP-1类似物可改善非酒精性脂肪肝的脂质代谢及胰岛素抵抗,该过程可能与PKCε有关。     

Regulation by chronic-mild stress of glucocorticoids, monocyte chemoattractant protein-1 and adiposity in rats fed on a high-fat diet

Stress has been reported as a widespread problem and several studies have linked obesity and inflammation-related diseases. Moreover, the combination of suffering from chronic stress and high energy intake might be related to the onset of some metabolic diseases. To study the possible relationships between stress, inflammatory status and obesity, a chronic-mild stress (CMS) paradigm with a high-fat dietary intake model (Cafeteria diet) was implemented on male Wistar rats for 11 weeks. Stress and dietary intake effects on animal adiposity, serum biochemical as well as glucocorticoids and inflammation markers were all analyzed. As expected, consuming a high-fat diet increased body weight, adiposity and insulin resistance in non-stressed animals. A decrease of total white adipose tissue (WAT) and an increase of fecal glucocorticoids, as well as angiotensinogen, and monocyte chemoattractant protein-1 (MCP-1) expression level in retroperitoneal WAT were found only on control-stressed rats. Regarding the serum MCP-1, a decrease was observed on animals under CMS while being fed Cafeteria diet. Furthermore, 11β-hidroxysteroid dehydrogenase activity, a glucocorticoid and obesity biomarker in the liver, was influenced by high-fat diet intake but not by stress. Finally, statistical analysis showed a strong relation between MCP-1 expression levels in retroperitoneal WAT, fecal corticosterone and total WAT. This trial proved that CMS induced a glucocorticoid-mediated response, which was reduced by the intake of a Cafeteria diet. These findings suggest that a high-fat diet could protect against a stress condition and revealed a different behavior to a stressful environment depending on the nutritional status.     

Effect of CCK antibodies on food intake and weight gain in Zucker rats

While exogenous administration of cholecystokinin (CCK) decreases food intake in many species, it has not been demonstrated conclusively that CCK is necessary for satiety to occur. In these experiments the role of CCK in eliciting satiety was further investigated by using endogenously produced and exogenously administered antibodies to CCK which were hypothesized to sequester circulating CCK. In the first experiment Zucker obese (n = 12, 192 +/- 16 g) and lean (n = 12, 152 +/- 11 g) male rats were administered CCK-8 conjugated to bovine serum albumin or bovine serum albumin by subcutaneous administration in Freund's adjuvant. Average percent binding of 125I-gastrin-17 by serum taken 4, 8 and 12 weeks after treatment initiation was increased (19.9 vs. 2.1, p less than 0.001) in rats treated with CCK conjugate than controls, and the increase was greater in lean (27.5 vs. 1.9) than in obese (12.2 vs. 2.2, p less than 0.001) rats. In lean, but not obese rats, average daily food intake and weight gain were increased (9 and 17% p less than 0.04 and p less than 0.02 respectively) in rats with CCK-AB compared with rats with no CCK-AB during the three months. Development of CCK-AB did not affect food intake response to exogenously administered CCK-8 or pancreas weight relative to body weight. In Experiment 2 increased food intakes of obese and lean rats 30 min after intraperitoneal injection of rabbit serum with CCK-AB were greater than those after intraperitoneal injection of rabbit serum without CCK-AB (1.92 vs. 1.41, g, p less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)     

脂质灌注对大鼠血浆抵抗素和ghrelin的影响*

目的：探讨脂质灌注对大鼠血浆抵抗素和ghrelin的影响。 方法： 采用正糖钳夹技术，在钳夹前后分别测定生理盐水对照组和脂质灌注组血浆抵抗素和ghrelin浓度，并用［3H］-葡萄糖作为示踪剂测定外周组织和肝糖的代谢。 结果： 脂质灌注组大鼠血浆游离脂肪酸（FFA）明显增加（P<0.01），葡萄糖输注率（GIR）明显降低（P<0.01）。对照组肝糖产率（HGP）明显被抑制（88%）。脂质输注组胰岛素对HGP的抑制作用明显减弱。在钳夹期间，脂质组与对照组比葡萄糖清除率（GRd）轻度降低。在正糖钳夹术结束时，对照组血浆ghrelin水平与钳夹前相比明显降低(P<0.05)。4 h的脂质灌注也引起了血浆ghrelin浓度的明显下降(P<0.05)，但是在钳夹结束时和对照组比没有明显差异。相关性分析表明空腹血浆ghrelin水平与空腹胰岛素和血糖呈明显负相关（r=-0.52和r=-0.61, P<0.05）。脂质灌注后大鼠血浆抵抗素水平较灌注前和对照组明显升高（P<0.01），空腹血浆抵抗素浓度与空腹FFA（r=0.68, P<0.01）、血糖（r=0.66, P<0.01）呈明显正相关。 结论： 脂质灌注诱导了肝脏和外周的胰岛素抵抗，抵抗素在胰岛素抵抗的形成中可能具有重要作用。高胰岛素血症，而不是游离脂肪酸，降低了大鼠循环ghrelin水平。     

Effect of hepatic vagotomy and/or coeliac ganglionectomy on the delayed eating response to insulin and 2DG injection in rats

The eating response that occurs following recovery from the effects of insulin or 2-deoxy-D-glucose (2DG) injection was examined in rats with hepatic vagotomy and/or coeliac ganglionectomy. Rats were deprived of food and injected with either saline (1 ml/kg), regular insulin (3 U/kg) or 2DG (200 mg/kg). Plasma glucose was measured periodically over the next 6 hr and then food was returned and intakes were measured over the next 2 hr. Rats increased food intake 6–8 hr after insulin or 2DG injection compared to the saline (control) condition. Nerve section did not affect the plasma glucose or food intake responses to insulin or 2DG injection. The results indicate that the innervation of the liver via the vagus nerve or coeliac ganglion is not involved in the delayed eating response to insulin and 2DG injection.     

胰升糖素样肽1对肥胖大鼠肝脏组织中Sesn2/AMPK/mTOR信号通路的干预效应

目的:研究胰升糖素样肽1受体激动剂利拉鲁肽对肥胖大鼠肝脏组织Sesn2/AMPK/mTOR信号通路的影响。方法:雄性SD大鼠随机分为正常饮食组(NC组)与高脂饮食组(HF组),喂养12周后,每组取5只评估肥胖大鼠模型建立。HF组再随机分为HF组、低剂量利拉鲁肽组(LG组)、中剂量利拉鲁肽组(MG组)与高剂量利拉鲁肽组(HG组),各组分别给予生理盐水及不同剂量利拉鲁肽(50、100和200μg/kg,皮下注射,每天2次) 4周。16周时测定体重及附睾脂肪指数;取大鼠肝脏组织HE染色观察肝脏脂肪变性情况; Western blot法检测肝脏组织中Sesn2、AMPK、p-AMPK、mTOR和p-mTOR的蛋白水平。结果:HF组大鼠的体重明显高于NC组(P 0. 01)。HF组肝脏细胞出现脂肪变性。与NC组相比,HF组的Sesn2蛋白水平明显降低(P 0. 01),p-AMPK/AMPK水平明显降低(P 0. 01),而p-mTOR/mTOR水平与NC组相比差异没有统计学显著性。利拉鲁肽干预4周后,药物处理组大鼠体重明显低于HF组(P 0. 01),MG与HG组大鼠的附睾脂肪指数较HF组降低(P 0. 01),肝组织脂肪变性较HF组减轻; HG组的Sesn2蛋白水平明显高于HF组(P 0. 01),MG与HG组的p-AMPK/AMPK水平较HF组明显升高(P 0. 01),LG组、MG与HG组p-mTOR/mTOR水平较HF组明显降低(P 0. 01)。结论:胰升糖素样肽1受体激动剂可能通过Sesn2/AMPK/mTOR信号通路影响机体能量代谢,改善肥胖状态。     

The anorectic response to growth hormone in obese rats is associated with an increased rate of lipid oxidation and decreased hypothalamic galanin

The aim of this study was to demonstrate differential effects of growth hormone (GH) on food intake in lean and obese rats and to investigate whether an anticipated anorectic response in obese rats might be associated with increased lipid oxidation and altered hypothalamic neuropeptide levels. GH (4 mg/kg/day) was administered during 5-21 days to non-obese and obese rats. Whereas GH stimulated food intake in the non-obese rats, the obese animals responded with a significantly (p < 0.05) suppressed food intake for 4-5 days. On day 4, the obese rats injected with GH and those injected with vehicle consumed 9.2 ± 0.66 g and 12.7 ± 1.05 g, respectively. The suppression of food intake was associated with significantly (p < 0.05) increased lipid oxidation. A similar, but statistically not verified, trend was seen in pair-fed rats not exposed to GH. However, while these animals appeared to economize their energy expenditure, the GH-exposed animals did not, thus creating a significant (p < 0.05) difference between these two groups. The increased lipid oxidation and energy expenditure observed in the rats exposed to GH were associated with significantly (p < 0.05) decreased levels of hypothalamic galanin (111 ± 33.2 pmol/g vs. those of the pair-fed controls: 228.5 ± 49.4 pmol/g). This difference was, however, not sustained. Thus, on day 21 both hypothalamic galanin and the food intake in the GH group were back to normal. Hypothalamic NPY remained unchanged by GH at all times. In conclusion, the present study suggests that increased lipid oxidation and decreased hypothalamic galanin are components in the mechanism by which GH inhibits food intake in an obese phenotype.