胰岛素抵抗大鼠肝脏组织p-IRE-1α的表达及意义

采用高脂饲料喂养并经高胰岛素-正常血糖钳夹技术评估,建立胰岛素抵抗大鼠模型.与正常饮食组相比,高脂饮食组大鼠血清游离脂肪酸和基础胰岛素水平升高(P＜0.05),平均葡萄糖输注率(GIR60-120)降低(P＜0.01),肝脏组织p-IRE-1α蛋白表达升高(P＜0.05).并且肝脏组织p-IRE-lα蛋白表达与血清游离脂肪酸水平呈正相关(r=0.627,P＜0.05).提示高脂饲料喂养可能通过升高血清游离脂肪酸水平,引起肝脏内质网应激,并通过p-IRE-1 α参与胰岛素抵抗的发生.

Abstract：

Fed with high-fat diet and assessed by hyperinsulinemia-euglycemia clamp technique, rat models with insulin resistance were successfully induced. Compared with normal chow group ( NC ), serum concentrations of free-fatty acids(FFAs) and baseline insulin in high-fat diet group(HF) was higher( P＜0.05 ), the average glucose infusion rate from 60 to 120 min( GIR60-120 ) was lower( P＜0.01 ), and the expression of p-IRE-lα in the liver was higher( P＜0.05 ). Furthermore, the expression of p-IRE-1α in the liver was positvely correlated with the serum concentration of FFAs. All these data indicate that high-fat diet may induce endoplasmic reticulum stress in the liver by elevating serum concentration of FFAs, and may participate in the genesis of insulin resistance via p-IRE-1α.     

非酒精性脂肪性肝病大鼠系统免疫及肠道免疫的变化

目的 观察在肥胖导致的非酒精性脂肪性肝病的进展过程中系统免疫及肠道免疫屏障的变化.方法 90只雄性SD大鼠均分为3组,即为正常饮食组、高糖饮食组、高脂饮食组,建立非酒精性脂肪性肝病大鼠模型,并于4、8、12周各组分别处死10只.肝脏HE染色观察肝脏脂肪变程度.鲎试验终点显色法检测门静脉血中内毒素水平.流式细胞术检测外周血单个核细胞及小肠集合淋巴结(PP结)中淋巴细胞CD4-CD8比值.结果 高糖饮食组在所有时间点内毒素水平均无显著升高,与正常饮食组差异均无统计学意义(P值均＞0.05).而高脂饮食组在8周时内毒素水平显著上升,与正常饮食组差异有统计学意义(P＜0.05).高糖饮食组与高脂饮食组在4周时外周血单个核细胞CD4/CD8显著高于正常饮食组(P值均＜0.05),至8周、12周时均显著低于正常饮食组(P值均＜0.05).PP结中CD4/CD8,高糖饮食组与高脂饮食组4、8周与外周血单个核细胞CD4/CD8变化趋势一致,12周时CD4/CD8与正常饮食组差异无统计学意义(P值均＞0.05).结论 肥胖可以抑制系统免疫及肠道免疫,肝脏可能参与调节肠道免疫.

Abstract：

Objective To study the changes of system immune and intestinal immune in the progression of non-alcoholic fatty liver disease due to obesity. Methods Ninty male SD rats were divided into control, high-sucrose and high-fat diet groups. Non-alcoholic fatty liver disease models were established by feeding with high-sucrose diet or high-fat diet and were killed at the 4th,8th and 12th weeks with 10 each for each group. The extent of liver steatosis was observed with HE staining.Portal blood endotoxin level was assessed by limulus test. The percentage of CD4+ and CD8+ cells in peripheral blood mononuclear cells (PBMC) and lymphocytes in Peyer's patches (PP) were calculated by flowcytometry. Results In comparison with control group, the endotoxin level was not elevated from the 4th week to 12th week in high-sucrose diet group, (all P values＞0.05), but was increased in high-fat diet group at the 8th week (P＜0.05). CD4/CD8 ratio in PBMC was higher in high-sucrose and higt-fat diet groups than that in control group at the 4th week (P＜0. 05) ,but was lower than that in control group at the 8th and 12th weeks (P＜0. 05). Whereas the variation of CD4/CD8 ratio in PP was consisted with that in PBMC between the high-sucrose and high-fat diet groups at the 4 th and 8 th weeks, but there was no difference when compared with control group at the 12 th week (P＞0.05).Conclusion Obesity can inhibit systematic immune and intestinal immune. The intestinal immune may be regulated by the liver.     

Hyperhomocysteinemia independently causes and promotes atherosclerosis in LDL receptor-deficient mice

Background Hyperhomocysteine is an independent risk factor of coronary heart disease （CHD）. However, whether hyperhomocys teine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the forma tion of atherosclerosis in low-density lipoprotein receptor-deficient （LDLr ） mice. Methods Forty-eight 7-week-old LDLr/ mice were assigned to the following groups： mice fed a standard rodent diet （control group）, mice fed a high-methionine diet （high-methionine group）, mice fed a high-fat diet （high-fat group）, and mice fed a diet high in both methionine and fat （high-methionine and high-fat group）. At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe. Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLrmice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.     

Effects of low-calorie diet on steatohepatitis in rats with obesity and hyperlipidemia

AIM: To evaluate the effects of low calorie diet (LCD) on nonalcoholic steatohepatitis (NASH) in rats with obesity and hyperlipidemia.METHODS: 29 Sprague-Dawley (SD) rats were randomly divided into three groups. The animals in control (n=9) and NASH group (n=10) were fed on standard rat diet and high fat diet respectively for 12 weeks, ten rats in LCD group were fed on high fat diet for 10 weeks and then low calorie diet for 2 weeks. At the end of the experiment, body weight, abdominal adipose content, liver function, and hepatopathological changes were examined to evaluate the effect of different feeding protocols on the experimental animals.RESULTS: There was no death of animal in the experimental period. All rats in the NASH group developed steatohepatitis according to liver histological findings. Compared with the control group, body weight (423.5±65.2 vs 351.1±43.0 g,P＜0.05), abdominal adipose content (14.25±1.86 vs9.54±1.43,P＜0.05), liver index (3.784-±0.533 vs2.957±±0.301%, P＜0.01),total serum cholesterol (1.60±0.41 vs 1.27±0.17 mmol/L, P＜0.05)and free fatty acids (728.2±178.5 vs 429.2±96.7 mmol/L,P＜0.01), serum alanine aminotransferase (1 257.51±671.34vs671.34±118.57 nkat/L, P＜0.05) and aspartic aminotransferse (2 760.51±998.66 vs 1 648.29±414.16 nkat/L, P＜0.01) were significantly increased in the NASH group. Whereas, when rats were fed on LCD protocol, their body weight (329.5±38.4 g,P＜0.01), abdominal adipose content (310.21±1.52 g, P＜0.05),liver index (3.199±0.552 %, P＜0.05), and serum alanine aminotransferase (683.03±245.49 nkat/L, P＜0.05) were significantly decreased, and the degree of hepatic steatosis (P＜0.05) was markedly improved compared with those in the NASH group. However, no significant difference was found in serum lipid variables and hepatic inflammatory changes between the two groups.CONCLUSION: LCD might play a role in the prevention and treatment of obesity and hepatic steatosis in SD rats,but it exerts no significant effects on both serum lipid disorders and hepatic inflammatory changes.     

Epidemiological study: Correlation between diet habits and constipation among elderly in Beijing region

AIM To investigate correlations between diet and prevalence of constipation among elderly people in Beijing.METHODS A total of 2776(≥ 60 years) were selected in Beijing region for investigation. Data regarding constipation and diet habits was collected via hierarchical status, segmentation and random cluster sampling. Investigation included constipation-related demographic indicators and diet habits. Door-to-door questionnaires and surveys included daily staple food intakes, frequency of fish, egg, fruits and vegetables consumption. Constipation was defined according to the China Chronic Constipation Diagnosis and Treatment Guideline(2013), with the following constipation judgment indicators: decreased defecation frequency, dry and hard stool, and difficulty in defecation.RESULTS The prevalence of constipation among elderly people in Beijing region was 13%. There was a positive correlation between prevalence of constipation and age, but negative correlations between prevalence of constipation and staple food, fish and dietary fibres(fruits and vegetables) intakes. These differences were all statistically significant.CONCLUSION The prevalence of elderly constipation in Beijing region is closely related to diet habits, and is significantly decreased by high staple foods intake, fish eating and high dietary fibres(fruits and vegetables) consumption.     

Impaired PI3K/Akt signal pathway and hepatocellular injury in high-fat fed rats

AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.     

中老年男性肥胖者阻塞性睡眠呼吸暂停低通气综合征与代谢综合征相关性研究

目的 探讨中老年男性肥胖者阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)与代谢综合征(metabolic syndrome,MS)及其组分之间的关系.方法 选择中老年男性肥胖患者154例,根据多导睡眠呼吸监测仪监测结果诊断OSAHS及病情严重程度,测定MS相关指标,应用统计学方法对OSAHS各组相关指标及OSAHS与MS之间的关系进行比较分析.结果 与对照组比较,重度OSAHS组高密度脂蛋白胆固醇明显降低[(1.03±0.29)mmol/L对(1.31±0.38)mmol/L,P＜0.05],血糖[(6.61±1.76)mmol/L对(5.47±0.64)mmol/L]、收缩压[(133±13)mm Hg对(125±12)mm Hg]及舒张压[(99±10)mm Hg对(80±5)mm Hg]明显升高(均P＜0.05);MS患病率轻度OSAHS组25.7%,中度OSAHS组46.5%,重度OSAHS组84.4%,均明显高于对照组16.1%(均P＜0.01);在OSAHS患者中,MS患病率是对照组的6.16倍.结论 中老年男性肥胖患者OSAHS是MS发病的独立危险因素.

Abstract：

Objective To explore the relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and metabolic syndrome (MS) in obese middle-aged and older men. Methods We selectively recruited 154 obese middle-aged and older men matched for body mass index (BMI) and age. The polysomnography was performed for diagnosing OSAHS and for discriminating disease severity. The BMI, waist circumference, blood pressure, plasma glucose and lipid profiles were measured and analyzed in all subjects. Appropriate statistical methods were used to compare the components of MS in each group. Logistic regression was taken to elucidate the relationship between OSAHS and MS. Results Compared to control group, severe OSAHS group had significantly lower high density lipoprotein cholesterol level [( 1.03 ± 0.29 ) mmol/L vs. ( 1.31 ± 0. 38) mmol/L,P＜0. 05] and higher fasting glucose [(6.61±1.76) mmol/L vs. (5.47±0.64) mmol/L, P＜0. 05]as well as higher systolic blood pressure [( 133 ± 13) mm Hg vs. ( 125 ± 12) mm Hg, P＜0. 05] and diastolic blood pressure [(99±10) mm Hg vs. (80±5) mm Hg, P＜0. 05]. The prevalence of MS was significantly higher in OSAHS group than in control group (mild OSAHS group: 25.7%,moderate OSAHS group: 46. 5%, severe OSAHS group: 84.4%, control group: 16. 1 %, all P＜0. 01). OSAHS was independently associated with an increased prevalence of MS Odds ratio, 6.16).Conclusions OSAHS is independently associated with MS in obese middle-aged and older men.     

A new formula for screening metabolic syndrome in Asians: skin fold thickness at A8 point on Erdheim diagram and waist circumference

Background and objectives Recent studies have shown that abdominal obesity is an important component for the diagnosis of metabolic syndrome (MS) and MS is a high risk factor for cardiovascular disease and diabetes mellitus. The aim of this study was to develop a new formula for screening and diagnosis of MS using the waist circumference (WC) and skin fold thickness at the point A8 (SFA8) on the Erdheim diagram. Methods A total of 358 essential hypertensive patients (189 male and 169 female) with a mean age of 59.0±9.7 years were included; 151 healthy people (79 male, 72 female) with a mean age of 57.3±12.1 years (similar to hypertensive patients) who were non-hypertensive and non-diabetic served as a control group. All subjects had no evidence of hepatic, renal, or endocrine disease as determined by history, physical examination and screening blood tests. Height, weight, WC, SFA8, blood pressure (BP), fasting plasma glucose, HDL-cholesterol and triglyceride levels were measured in all subjects. Abdominal obesity measured by WC using the Asia-Pacific criteria (IDFA) was applied for meeting the MS definition. The normal value of SFA8 was measured in the non- MS group. Relationships between SFA8 and systolic BP, diastolic BP, fasting plasma glucose, HDL-cholesterol and triglyceride levels were calculated in the control group. A new formula was developed according to high SFA8 and high WC. Results The normal value of SFA8 in non-MS group was 23.6±7.2 mm in male and 26.5±4.6 mm in female, respectively. The value of SFA8 in MS group was 36.7± 7.4 mm in male and 38.9 ± 8.1 mm in female, respectively. The value of WC in MS group and non-MS group were 92.5±3.0 cm and 79.4±6. 1 cm in male and 86.3±6.4 cm and 74.7±5.4 cm in female, respectively. There was a correlation between SFA8 and systolic BP, diastolic BP, fasting plasma glucose, HDL-cholesterol and triglyceride in control group (the correlation coefficients were 0.29, 0.23, 0.25, -0.31 and 0.46, respectively, P < 0.01). A new formula for MS was suggested as high WC (≥ 90 cm in male, ≥ 80 cm in female) high SFA8 (≥ 30 mm). The sensitivity, specificity, false positive rate, false negative rate, positive predictive value, and negative predictive value of the new formula assessed with the IDFA definition were 94%, 93%, 7%, 6%, 92% and 95%, respectively. The percentage of all patients who met the criteria for MS by conventional definition was 46.2%. The percentage of all patients who met the criteria by the new definition was 47.0%. There was no difference between the prevalence percentage of the MS according to new criteria and the IDFA criteria in all patients, in male and in female, respectively (P > 0.05). Conclusion This new formula for MS might be useful for easy screening. The advantage over current criteria is the lack of need for laboratory testing.     

Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease

BACKGROUND In non-alcoholic fatty liver disease(NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD.AIM To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.METHODS The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing(51 CrEDTA).RESULTS Twenty Caucasian patients, 90% male, median age 43 years, body mass index(BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight(-5.3 ± 4.1 kg,P = 0.003), mean waist circumference(-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase(ALT)-28.3 ± 11.9 IU/L, P =0.0001; aspartate aminotransferase(AST)-6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline(mean percentage retention of51 Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet.CONCLUSION Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.     

老年人血镁水平降低与血糖代谢异常的关系

Objective To explore the relationship between serum magnesium (Mg) levels and glucose metabolism disorders in the elderly.Methods The data of health examination of 126 elderly people were collected in our hospital.There were 50 patients with type 2 diabetes,35 patients with impaired glucose regulation (IGR) and 41 people with normal glucose.The clinical data of the three groups were compared and analyzed.Results (1)There were no significant differences in age,body mass index (BMI) and blood lipid level among the three groups.The mean serum Mg level was lower in normal glucose group [(0.84±0.1) mmol/L] than in diabetic group [(0.75±0.11) mmol/L,P＜0.01] and IGR group [(0.78±0.12) mmol/L,P＜0.05].(2)The prevalence of hypomagnesemia was higher in diabetic group and IGR group than in normal glucose group (24%,28.6% vs.7.3%,P＜ 0.01 ).(3)The correlation study showed that the serum magnesium level was negatively associated with fasting plasma glucose and HbA1c (r= - 0.343,- 0.271,P＜0.01 ),but not associated with age and BMI.Conclusions The low serum magnesium level is associated with glucose metabolism disorders in the elderly.     

新疆维吾尔自治区汉、维吾尔和哈萨克族人群颈动脉内中膜厚度的流行病学调查

目的 了解新疆维吾尔自治区汉、维吾尔和哈萨克族35岁及以上人群颈动脉内中膜厚度(intima-media thickness,IMT)及其相关危险因素.方法 采用整群随机抽样方法抽取新疆维吾尔自治区汉、维吾尔和哈萨克族35岁及以上居民进行颈动脉IMT及其相关危险因素的横断面调查.结果 新疆维吾尔自治区35岁及以上人群的颈动脉IMT汉族为(0.0761±0.0283)cm,维吾尔族为(0.0663±0.0262)cm,哈萨克族为(0.0781±0.0274)cm,不同民族之间的IMT差异均有统计学意义(均P＜0.05).汉族颈动脉IMT男性为(0.0807±0.0288)cm,女性为(0.0717±0.0270)cm(P＜0.01);维吾尔族颈动脉IMT男性为(0.0706±0.0270)cm,女性为(0.0633±0.0252)cm(P＜0.01);哈萨克族颈动脉IMT男性为(0.0794±0.0280)cm,女性为(0.0768±0.0268)cm(P＜0.01).简单线性相关分析显示,新疆维吾尔自治区汉、维吾尔和哈萨克族人群年龄、收缩压、舒张压、空腹血糖、总胆固醇、踝臂指数与颈动脉IMT相关(r值分别为0.176,0.168,0.167,0.053,0.097和0.067,均P＜0.05).结论 新疆维吾尔自治区哈萨克族的颈动脉IMT大于汉族和维吾尔族.IMT与年龄、收缩压、舒张压、空腹血糖、总胆固醇、踝臂指数相关.

Abstract：

Objective To investigate carotid artery intima-media thickness (IMT) and the correlated risk factors in Han, Uygur, Hazakh residents over 35 years old of Xinjiang Uygur autonomous region. Method Cross-sectional and cluster sampling random selected method was carried out for residents over 35 years old in Han, Uygur, Hazakh population of Xinjiang to investigate IMT and correlated risk factors. Results IMT of Han, Uygur, Hazakh residents over 35 years old of Xinjiang Uygur autonomous region was (0. 0761 ± 0. 0283 ) cm, (0. 0663 ± 0. 0262) cm, and (0. 0781 ± 0. 0274 ) cm, respectively. There were significantly difference between various nationality( all P ＜0. 05 ). IMT was thicker in male Han people than in female Han people [(0. 0807 ± 0. 0288 )cm vs. (0. 0717 ± 0. 0270 ) cm, P ＜ 0. 01] and in male Uygur than in female Uygnr residents [(0. 0706 ±0. 0270)cm vs. (0. 0633 ±0. 0252)cm, P ＜0. 01]and in male Hazakh and female Hazakh residents [(0. 0794 ± 0. 0280) cm vs. (0. 0768 ± 0. 0268 ) cm, P ＜ 0. 01].Linear correlation analysis showed that age ( r = 0. 176, P ＜ 0. 05 ), systolic blood pressure ( r = 0. 168, P ＜ 0. 05 ), diastolic blood pressure ( r = 0. 167, P ＜ 0. 05 ), fasting blood glucose ( r = 0. 053, P ＜ 0. 05 ), total cholesterol(r = 0.097,P ＜ 0.05) and ankle brachial index (r = 0.067, P ＜ 0.05) were significantly correlated with IMT. Conclusions Our results showed that IMT was thicker in Hazakh residents than in Han and Uygnr residents. IMT was closely related to known cardiovascular risk factors including age,systolic blood pressure,diastolic blood pressure,fasting blood glucose, total cholesterol and ankle brachial index level.     

A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome

Objective

Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project.

Methods and design

Clinical intervention study: the patients (n = 337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). Measurements: the effects on MetS risk criteria were recorded before and after the intervention period.

Results

An enlarged waist circumference (≥88 cm for women and ≥102 cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85 mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (≥5.55 mmol/L), 51% were hypertriacylglycerolemic (≥1.7 mmol/L), and 72% had low HDL cholesterol (<1.0 mmol/L for men, and <1.3 mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p < 0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p < 0.028).

Conclusions

The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets.     

高脂喂养及罗格列酮干预对老年大鼠骨骼肌线粒体功能的影响

目的 观察高脂饮食和罗格列酮干预对老年大鼠骨骼肌过氧化物酶体增生物激活受体γ共激活因子1α(PGC-1α)和线粒体融合蛋白2(Mfn2)表达的影响. 方法 21～23月龄Wistar大鼠分为老年对照组、高脂组和高脂+罗格列酮干预组(干预组),并设4～5月龄Wistar大鼠作为青年对照组.应用正常葡萄糖高胰岛素钳夹技术评价胰岛素敏感性,高脂喂养第8周时,检测骨骼肌PGC-1α和Mfn2的mRNA及蛋白表达.结果高脂喂养8周后,青年对照组、老年对照组和高脂组空腹血游离脂肪酸[(0.68±0.18)mmol/L、(0.82±0.23)mmol/L和(1.53±0.40)mmol/L],三酰甘油[(0.53±0.13)mmol/L、(0.63±0.17)mmol/L和(1.08±0.30)mmol/L],骨骼肌三酰甘油[(1.09±0.17)mmol/L、(1.34±0.20)mmol/L和(2.07±0.30)mmol/L]均升高,葡萄糖输注率((30.4±4.2)mg·kg~(-1)·min~(-1)、(20.9±2.2)mg·kg~(-1)·min~(-1)和(12.0±1.9)mg·kg~(-1)·min~(-1)]下降;经过罗格列酮干预后游离脂肪酸[(0.93±0.29)mmol/L]、三酰甘油[(0.62±0.12)mmol/L]及骨骼肌三酰甘油[(1.68±0.28)mmol/L)]均明显下降,葡萄糖输注率[(16.7±1.7)mg·kg~(-1)·min~(-1)]升高.与青年对照组比较,老年对照组骨骼肌PGC-1α和Mfn2的表达下降,经高脂喂养后PGc-1α和Mfn2的表达进一步下降,干预组上述基因的表达均显著高于高脂组(P<0.05),但仍比老年对照组降低(P<0.05). 结论 高脂饮食可诱导老年大鼠产生IR,推测可能与骨骼肌PGC-1α和Mfn2的表达下降有关;罗格列酮可通过改变骨骼肌PGC-1α和Mfn2的表达增加胰岛素敏感性.     

运动对高脂饮食诱导肥胖大鼠过氧化物酶体增长因子活化受体-δ表达和胰岛素抵抗的影响

研究运动对高脂饮食诱导的肥胖大鼠肌肉和脂肪组织中过氧化物酶体增长因子活化受体-δ（PPAR-δ）表达的影响,并探讨其改善胰岛素抵抗的可能机制.方法 取体质量135～150 g的9周龄雄性Wistar大鼠80只,随机数字表法取其中60只6周时间饲以高脂饲料用于制作肥胖大鼠模型,另20只饲以普通饲料.将54只造模成功肥胖大鼠随机分为高脂饮食组（HFD）、高脂饮食同时运动组（E-HFD）、高脂饮食后运动组（HFD-E）,每组18只,同时从普通饲料饲养大鼠中随机选择16只作为正常饮食组（RD）.按文献标准对各组大鼠进行6周运动训练.检测比较各组游泳运动训练后体质量、肿瘤坏死因子（TNF）-α、瘦素、白细胞介素（IL）-1的水平以及空腹血糖、空腹胰岛素并计算胰岛素敏感指数（ISI）,采用实时定量聚合酶链反应（RT-PCR）检测肌肉和脂肪组织中PPAR-δ、葡萄糖转运蛋白（GLUT）-4、磷酸肌醇3激酶（PI3K）mRNA的表达,并采用Western blot法检测肌肉和脂肪组织中PPAR-δ蛋白的表达水平.组间数据比较采用双侧t检验.结果 HFD组ISI为1.13±0.21,相比HFD组,E-HFD组和HFD-E组的IS1分别提高了 71.1%和45.7%（分别为2.09±0.32和1.80±0.34）,而HFD-E组低于E-HFD组,差异均有统计学意义（均P＜0.05）.HFD组TNF-α水平为（101±24）ng/L,相比HFD组,E-HFD组和HFD-E组则分别下降了20.0%和9.2%[分别为（81±16）和（92±19）ng/L],差异均有统计学意义（P＜0.05）.与HFD组相比,E-HFD组和HFD-E组瘦素和IL-I水平均有显著下降（均P＜0.05）.与HFD组相比,E-HFD组和HFD-E组骨骼肌和脂肪中PPAR-δ、GLUT-4、PI3K mRNA的表达均显著升高,差异均有统计学意义（均P＜0.05）,且在E-HFD组变化尤为显著（均P＜0.01）.与HFD组相比,E-HFD组骨骼肌和脂肪组织中PPAR-δ蛋白表达分别升高了388.4%和203.2%（均P＜0.05）;HFD-E组骨骼肌和脂肪组织中PPAR-δ蛋白的表达则分别升高了272.9%和117.9%（均P＜0.05）.结论 运动降低了高脂饮食诱导的肥胖大鼠的血清脂肪因子瘦素、TNF-α和IL-1水平,改善了胰岛素抵抗,可能是通过上调肌肉和脂肪组织中PPAR-δ的表达发挥作用.     

Influence of dietary fat intake on bodyweight and risk of obesity among Chinese adults, 1991–2015: a prospective cohort study

Background

China has experienced an unprecedented rapid modernisation, major changes in diet and physical activity behaviours, and a rapid increase in prevalence of obesity. Although prevailing weight-loss guidelines recommend a fat-restricted and calorie-restricted diet, the associations between fat intake and risk of obesity have been inconsistent from epidemiological and clinical-trial evidence. We aimed to examine the influence of dietary fat on bodyweight and the risk of overweight and obesity among Chinese adults over time.

Effects of monounsaturated fatty acids v complex carbohydrates on serum lipoproteins and apoproteins in healthy men and women

The effects of a high-carbohydrate, high-fiber diet and an olive-oil-rich diet on the distribution of cholesterol over the various lipoproteins, on serum apolipoproteins, and on the composition of HDL2 and HDL3 were studied under strict dietary control. Forty-eight healthy subjects first consumed a high-saturated-fat diet [proportion of energy, en%] (saturated fat 20 en%, total fat 38 en%) for 17 days. For the next 36 days, 24 subjects consumed a diet high in complex carbohydrates (monounsaturated fat 9 en%, total fat 22 en%) and the other 24 consumed a high-fat, olive-oil-rich diet (monounsaturated fat 24 en%, total fat 41 en%). The amounts of protein (12% to 14 en%), polyunsaturated fat (4 to 5 en%), and cholesterol (31 to 35 mg/MJ) were similar in all three diets. Serum cholesterol levels fell by 0.44 mmol/L in subjects consuming the carbohydrate diet and by 0.52 mmol/L for those receiving the olive-oil-rich diet. VLDL-cholesterol levels rose by 0.08 mmol/L in the carbohydrate group and fell by 0.08 mmol/L in the olive oil group (P less than .05 for difference between test diets). HDL2 and LDL cholesterol levels fell to the same extent on both diets. HDL3 cholesterol fell by 0.09 mmol/L on the high-carbohydrate diet and increased by 0.01 mmol/L on the olive oil diet (P less than .05). There was no change in the composition of HDL3, suggesting that the fall was due to a decrease in the total number of circulating particles.(ABSTRACT TRUNCATED AT 250 WORDS)     

A low-carbohydrate/high-fat diet improves glucoregulation in type 2 diabetes mellitus by reducing postabsorptive glycogenolysis

The aim of this study was to examine the mechanisms by which dietary carbohydrate and fat modulate fasting glycemia. We compared the effects of an eucaloric high-carbohydrate (89% carbohydrate) and high-fat (89% fat) diet on fasting glucose metabolism and insulin sensitivity in seven obese patients with type 2 diabetes using stable isotopes and euglycemic hyperinsulinemic clamps. At basal insulin levels glucose concentrations were 148 +/- 11 and 123 +/- 11 mg/dl (8.2 +/- 0.6 and 6.8 +/- 0.6 mmol/liter) on the high-carbohydrate and high-fat diet, respectively (P < 0.001), with insulin concentrations of 12 +/- 2 and 10 +/- 1 microIU/ml (82 +/- 11 and 66 +/- 10 pmol/liter) (P = 0.08). Glucose production was higher on the high-carbohydrate diet (1.88 +/- 0.06 vs. 1.55 +/- 0.05 mg/kg.min (10.44 +/- 0.33 vs. 8.61 +/- 0.28 micromol/kg.min) (P < 0.001) because of higher glycogenolysis. Gluconeogenic rates were not different between the diets. During the use of hyperinsulinemic euglycemic clamps, insulin-mediated suppression of glucose production and stimulation of glucose disposal were not different between the diets. Free fatty concentrations were suppressed by 89 and 62% (P < 0.0001) on the high-carbohydrate and high-fat diet, respectively. We conclude that short-term variations in dietary carbohydrate to fat ratios affect basal glucose metabolism in people with type 2 diabetes merely through modulation of the rate of glycogenolysis, without affecting insulin sensitivity of glucose metabolism.     

肥胖大鼠血脂和体脂肪变化及心室肌细胞内钙离子强度与心律失常发生的关系

目的 观察高脂饮食诱导肥胖(DIO)大鼠血脂和体脂肪变化,探讨心室肌细胞内钙离子强度与心律失常发生的关系.方法 健康雄性SD大鼠60只,体质量200～250 g.将大鼠按体质星随机分为对照组(15只)和高脂饮食组(45只),高脂饮食组采用高脂饮食诱导法建立肥胖大鼠模型.喂养12周后,在高脂饮食组筛选体质量增加明显的大鼠进入肥胖组(15只).两组各选8只大鼠舌下注射0.1 ms/kg BaCl2,诱导心律失常.应用标准Ⅱ导联心电图连续监测1 h,评价大鼠心律失常发生率及严重程度.采集两组大鼠腹主动脉血,分离血清,测血清总胆同醇,甘油三酯,低密度脂蛋白胆固醇和高密度脂蛋白胆固醇.分离大鼠肾周脂肪,睾周脂肪和肠系膜脂肪,称重,计算体脂比.酶解法分离大鼠单个心室肌细胞,应用激光共聚焦技术记录细胞内钙离子强度([Ca2+]i).结果 肥胖组大鼠体脂比[(7.71±0.74)%]明显高于对照组[(4.69±0.37)%],两组比较差异有统计学意义(t＝3.650,P＜0.05),血清总胆固醇,甘油三酯和低密度脂蛋白水平,肥胖组[(1.26±0.04),(0.58±0.10),(0.51±0.04)mmol/L]与对照组[(0.92±0.08),(0.29±0.03),(0.31±0.04)mmol/L]比较显著增高(t值分别为3.801,2.778,3.536,P＜0.05),肥胖组大鼠心律失常发生率高于对照组(X2＝5.333,P＜0.05),心律失常评分肥胖组(2.5±0.6)高于对照组(0),肥胖组大鼠心室肌细胞内钙离子强度(247.96±20.03)明显高于对照组(174.25±23.13),两组比较差异有统计学意义(t=2.409,P＜0.05).结论 肥胖大鼠心律失常发生率增加,血脂升高,心肌细胞内钙离子积聚是引发肥胖源性心律失常的主要机制之一.     

老年2型糖尿病并存非酒精性脂肪性肝病患者体成分及危险因素分析

目的 对老年2型糖尿病合并与未合并非酒精性脂肪性肝病患者体成分、血脂、腹型肥胖和代谢综合征发生率等进行比较,探讨合并非酒性脂肪性肝病的可能危险因素.方法 将入选老年2型糖尿病患者分为合并非酒精性脂肪性肝病组(脂肪肝组)83例及未合并非酒精性脂肪性肝病组(非脂肪肝组)85例,比较两组体成分、血脂、腹型肥胖和代谢综合征发生率等临床资料. 结果 脂肪肝与非脂肪肝组比较,组体质指数[(26.9±2.5)kg/m~2对(24.1±2.5j)kg/m~2,P=0.000]、腰臀围比(0.92±0.07对0.87±0.06,P=0.000)、总体脂肪比[(29.6±6.6)%对(25.3±5.5)%,P=0.000]、腹部脂肪[(11.0±2.5)kg对(8.7±2.3)kg,P=0.000]、内脏脂肪[(3.0±0.7)kg对(2.3±0.6)kg,P=0.000]、内脏脂肪面积[(97.6±22.2)cm~2对(75.5±21.1)cm~2,P=0.000]、三酰甘油[(1.98±0.94)mmol/L对(1.22±0.61)mmol/L,P=0.000]均升高,高密度脂蛋白胆醇[(1.23±0.32)mmol/L对(1.40±0.37)mmol/L,P=0.002]水平降低,差异均有统计学意义;体脂过高(68.7%对36.5%,P=0.000)、血脂异常(47.0%对21.2%,P=0.000)、腹型肥胖(69.9%对43.5%,P=0.001)和代谢综合征(49.4%对9.6%,P=0.000)的发病率亦明显升高,差异均有统计学意义;而总胆醇[(4.93±0.94)mmol/L对(4.73±1.07)mmol/L,P=0.219]和低密度脂蛋白胆固醇[(3.23±0.80)mmol/L对(3.07±0.89)mmol/L,P=0.229]两组比较,差异无统计学意义.Logistic回归分析显示体质指数超标(β=1.268,P=0.000,OR=3.56)、总体脂肪比过高(β=0.902,P=0.023,OR=2.47)和代谢综合征(β=1.664,P=0.000,OR=5.28)与老年2型糖尿病患者合并非酒精性脂肪性肝病相关. 结论 体质指数超标、总体脂肪比过高与老年2型糖尿病患者合并非酒精性脂肪性肝病相关,非酒精性脂肪性肝病可能是代谢综合征的一个组成部分.