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1.
目的:筛查在正常人、单纯性肥胖患者及肥胖伴2型糖尿病患者内脏脂肪组织中差异表达的基因。方法:利用自制的高密度cDNA芯片,比较正常人、单纯性肥胖患者及肥胖伴2型糖尿病患者内脏脂肪组织中差异表达的基因,以寻找脂肪组织特异的与肥胖及糖尿病发生有关的基因。结果:和正常人相比,在肥胖患者及肥胖伴2型糖尿病患者中上调的基因分别有119个和257个,下调的基因分别有46和58个。这些基因中有77个在两组中均上调,其中包括与代谢有关的基因,如丙酮酸脱氢酶激酶4(PDK4)以及窖蛋白、金属硫因蛋白等;8个基因在两组中均下调,其中包括脂肪合成途径中的关键酶,如3-羟基-3-甲基戊二酸单酰辅酶A(MGA)合成酶、脂肪酸合成酶及硬脂酰辅酶A脱氢酶。另外,酪氨酸-3单加氧酶-色氨酸-5单加氧酶活化蛋白θ(YWHAZ)仅在肥胖伴2型糖尿病患者中上调,而在单纯性肥胖患者中不变,该基因所编码的蛋白在胰岛素信号转导途径中起着负调控的作用。结论:脂肪组织中脂肪生成下降、脂肪酸氧化增加可能是肥胖及2型糖尿病中胰岛素抵抗发生的共同原因,其它基因功能的改变也可能参与了肥胖及2型糖尿病的发生,而胰岛素信号转导受阻可能是肥胖向糖尿病转化的促进因素。对这些基因的进一步研究将有助于更好地了解肥胖及糖尿病的发生机制。  相似文献   

2.
SJÖSTRÖM, c. DAVID, LAUREN LISSNER, HANS WEDEL, and LARS SJÖSTRÖM. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study. Obes Res. Objective: To examine the effect of a large, long standing and intentional weight reduction on the incidence of diabetes, hypertension and lipid disturbances in severely obese individuals as compared to weight-stable obese controls. Research Methods and Procedures: The ongoing prospective SOS (Swedish Obese Subjects) intervention consists of a surgically treated group and a matched control group obtaining conventional obesity treatment. This report is based on 845 surgically treated patients and 845 controls (BMI41. 0±4. 6 kg/m2 (mean±standard deviation [S])) followed for 2 years. Results: Surgically treated patients lost 28±15 kg and controls 0. 5±8. 9 kg (p<0. 0001). Two-year incidence of hypertension, diabetes, hyperinsulinemia, and lipid disturbances was compared in the two treatment groups. Adjusted odds ratios (95% CI) for the surgically treated group versus controls were 0. 38 (0. 22, 0. 65) for hypertension, 0. 02 (0. 00, 0. 16) for diabetes, 0. 10 (0. 03, 0. 28) for hyperinsulinemia, 0. 10 (0. 04, 0. 25) for hypertriglyceridemia, 0. 28 (0. 16, 0. 49) for low HDL-cholesterol and 1. 24 (0. 84, 1. 8) for hypercholesterolemia. Compared to controls, the 2-year recovery rates from hypertension, diabetes, hypo-HDL, and hypertriglyceridemia were significantly higher in the surgically treated group. Discussion: Intentional weight loss in the obese causes a marked reduction in the 2-year incidence of hypertension, diabetes and some lipid disturbances. The results suggest that severe obesity can and should be treated.  相似文献   

3.
The Katalyst intervention program was piloted in fifth-grade classrooms at two Appalachian schools during the 2017–18 academic year as a potential educational resource to tackle the rising rates of obesity and chronic diseases in this region. The program consisted of four 60-minute modules, each based on a specific organ system. Each module incorporated hands-on lessons in physiology with an emphasis on preventing chronic disease through diet, nutrition, physical activity, and abstinence from drug and tobacco use. The modules were led by medical students and undergraduate volunteers who completed a two-day training. A 37-item survey assessing knowledge and perceptions regarding healthy lifestyles was administered to fifth grade participants prior to and following the intervention in order to assess the impact of the program. Additionally, educators at intervention schools were given a questionnaire post-intervention to provide feedback on the program. This paper describes the rationale, program design and execution, and conclusion of the Katalyst intervention program. It is anticipated that this program will reinforce current educational standards regarding diet, nutrition and physical activity in order to empower target students to establish healthy lifestyle behaviors and that programs modeled after the Katalyst curriculum may serve as a novel, viable option to health educators.  相似文献   

4.
SJÖSTRÖM, C DAVID, LAUREN LISSNER, LARS SJÖSTROM. Relationships between changes in body composition and changes in cardiovascular risk factors: The SOS Intervention Study. Relationships between 2-year changes in body composition (estimated from computed tomography-validated anthropometry based on sagittal trunk diameter, weight, and height), adipose tissue (AT) distribution, and cardiovascular risk factors (blood pressure, lipids, glucose, insulin, uric acid) were examined in 842 treated adults with severe obesity with weight changes from ?95. 5 to +30. 6 kg. Although the change (Δ) of visceral AT mass (expressed in % total AT) for a given change in body mass index (ΔBMI) was 6-fold larger in men than in women, Δwaist and Δwaist/hip were similar in both sexes. In men, risk factor changes were similarly related to Awaist, Abodyweight, and ΔBMI, whereas in women, Δbodyweight seemed to be the single independent variable with the highest explanatory power. In multivariate regressions adjusted for ΔBMI and baseline conditions, Δvisceral AT mass was more strongly associated with risk factor changes than were Δwaist and ?waist/hip. When using a three-compartment model (lean body mass, subcutaneous and visceral AT masses) plus neck and thigh girths (indicators of subcutaneous AT distribution), risk factor changes were related both to ?subcutaneous and ?visceral AT masses but not to Δlean body mass. In agreement with cross-sectional findings, Δneck was positively and Δthigh was negatively related to some risk factor changes. Thus, the use of waist as a single risk factor indicator seems less effective for epidemiological studies than the simple anthropometric measures presented here, which are able to separate the effects of visceral AT mass, subcutaneous AT mass, and subcutaneous AT distribution on metabolic parameters under both cross-sectional and longitudinal conditions.  相似文献   

5.
We investigated the effect of dietary Korean proso-millet protein concentrate (PMP) on glycemic responses, plasma lipid levels, and the plasma level and gene expression of adiponectin in obese type 2 diabetic mice under normal and high-fat feeding conditions. The findings were that the feeding of PMP clearly elevated plasma high-density lipoprotein cholesterol (HDL cholesterol) and adiponectin levels and brought about effective reduction in the levels of glucose and insulin in mice under high-fat diet conditions as compared with a control diet. Gene expression study revealed that the diet up-regulated expression of adiponectin and down-regulated tumor necrosis factor-α (TNF-α). Considering the central role of adiponectin and HDL cholesterol in improving and ameliorating type 2 diabetes, obesity, and cardiovascular disease, our findings imply that PMP may have potential for therapeutic intervention in type 2 diabetes.  相似文献   

6.
《Free radical research》2013,47(4):243-256
Abstract

Diabetes mellitus and breast cancer are two important health problems. Type 2 diabetes (T2DM) and obesity are closely linked with both being associated with breast cancer. Despite abundant epidemiological data, there is no definitive evidence regarding the mechanisms responsible for this association. The proposed mechanisms by which diabetes affects breast cancer risk and prognosis are the same as the mechanisms hypothesised for the contribution of obesity to breast cancer risk. The obesity-induced inflammation promoted by adipose tissue dysfunction is a key feature, which is thought to be an important link between obesity and cancer. Inflammation induces an increase in free radicals and subsequently promotes oxidative stress, which may create a microenvironment favourable to the tumor development in obese persons. Oxidative stress is also proposed as the link between obesity and diabetes mellitus. Therefore, obesity-related oxidative stress could be a direct cause of neoplastic transformation associated with obesity and T2DM in breast cancer cells. This review is focused on the role of obesity-related oxidative stress in the context of chronic inflammation, on the time of breast cancer onset and progression, which provide targets for preventive and therapeutic strategies in the fields of diabetes and obesity-related breast cancer.  相似文献   

7.
哺乳动物体内存在着褐色脂肪组织。有别于白色脂肪组织储存能量的功能,褐色脂肪组织的主要功能是通过产热作用来维持机体的能量代谢平衡。陆续有研究阐明调控褐色脂肪组织分化与能量代谢过程的分子机制,逐渐揭示了褐色脂肪组织分化与能量代谢过程中涉及的信号通路与转录调控。这不仅让我们更好地理解褐色脂肪组织在能量代谢调控中的重要作用,而且为基于褐色脂肪组织的肥胖治疗提供了理论依据。本文阐述了近年来研究发现的褐色脂肪组织分化与代谢过程中发挥重要作用的信号通路与转录调控,并讨论了多种基于针对褐色脂肪组织的肥胖治疗手段的有效性与可行性。  相似文献   

8.
Objective : To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. Research Methods and Procedures : Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuouswave Doppler examinations. Results : At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 ±10.1%, which was significantly (p<<0.001) smaller than their 1-year loss of 17.1 ±8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 ± 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 ± 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. Discussion : Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.  相似文献   

9.
We examined the effects of three high-fat diets (HFD), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, and 24%) but identical in total fat (40%), on body composition, macrophage behavior, inflammation, and metabolic dysfunction in mice. Diets were administered for 16 weeks. Body composition and metabolism [glucose, insulin, triglycerides, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), total cholesterol (TC)] were examined monthly. Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators [Toll-like receptor (TLR)-2, TLR-4, MCP-1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, suppressor of cytokine signaling (SOCS)1, IFN-γ] was measured along with activation of nuclear factor kappa-B (NFκB), c-Jun N-terminal kinase (JNK), and p38- mitogen-activated protein kinase (MAPK). AT macrophage infiltration was examined using immunohistochemistry. Circulating MCP-1, IL-6, adiponectin, and leptin were also measured. SF content, independent of total fat, can profoundly affect adiposity, macrophage behavior, inflammation, and metabolic dysfunction. In general, the 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity, macrophage infiltration, and insulin resistance (IR), whereas the 6%-SF and 24%-SF diets produced lower levels of these variables, with the 24%-SF diet resulting in the least degree of IR and the highest TC/HDL-C ratio. Macrophage behavior, inflammation, and IR following HFD are heavily influenced by dietary SF content; however, these responses are not necessarily proportional to the SF percentage.  相似文献   

10.
Recently, vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. In this study, we examined whether vaspin mRNA expression is a marker of visceral obesity and correlates with anthropometric and metabolic parameters in paired samples of visceral and subcutaneous adipose tissue from 196 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance. Vaspin mRNA expression was only detectable in 23% of the visceral and in 15% of the subcutaneous (SC) adipose tissue samples. Vaspin mRNA expression was not detectable in lean subjects (BMI<25) and was more frequently detected in patients with type 2 diabetes. No significant correlations were found between visceral vaspin gene expression and visceral fat area or SC vaspin expression. However, visceral vaspin expression significantly correlates with BMI, % body fat, and 2 h OGTT plasma glucose. Subcutaneous vaspin mRNA expression is significantly correlated with WHR, fasting plasma insulin concentration, and glucose infusion rate during steady state of an euglycemic-hyperinsulinemic clamp. Multivariate linear regression analysis revealed % body fat as strongest predictor of visceral vaspin and insulin sensitivity as strongest determinant of SC vaspin mRNA expression. In conclusion, our data indicate that induction of human vaspin mRNA expression in adipose tissue is regulated in a fat depot-specific manner and could be associated with parameters of obesity, insulin resistance, and glucose metabolism.  相似文献   

11.
PEKKARINEN, TUULA, PERTTI MUSTAJOKI. Use of very low-calorie diet in preoperative weight loss: Efficacy and Safety. We report the efficacy of a very low-calorie diet (VLCD)-based weight reduction program in patients with morbid obesity whose elective surgery had been postponed because of being overweight. The safety of weight loss on the immune system will also be evaluated. Thirty patients (mean age, 50 years; weight, 125 kg; BMI, 44 kg/m2) were treated. The program consisted of a 7-week to 24-week VLCD period, supported by individual sessions with a therapist, and of a refeeding period of 1 month before surgery. Two patients discontinued, and the mean weight loss of the remaining 28 patients was 19. 6 kg (15% of initial weight). In 23 patients, weight loss was 10% or more of the initial weight. After weight loss, 15 patients underwent surgery, 4 patients did not need an operation, and the remaining 9 patients were not operated on for various reasons. The numbers of circulating leukocytes, neutrophils, basophils, monocytes, CD3+, CD4+, CD8+, and natural killer cells did not change significantly by the ninth week on VLCD or by the end of the program. However, there was a significant (p<0. 05) decrease in the immunoglobulinM serum concentration during the program. In conclusion, a VLCD program is suitable for preoperative weight reduction in morbid obesity and seems not to compromise the immune system.  相似文献   

12.
13.
The recently discovered uncoupling protein 3 (UCP3) is highly homologous to the mitochondrialinner membrane protein UCP1, which generates heat by uncoupling the respiratory chainfrom oxidative phosphorylation. The thermogenic function of UCP1 protects against cold andregulates the energy balance in rodents. We review in vitro studies investigating the uncouplingactivity of UCP3 and in vivo studies, which address UCP3 gene expression in brown adiposetissue and skeletal muscle under various metabolic conditions. The data presented are, for themost, consistent with an uncoupling role for UCP3 in regulatory thermogenesis. We alsodiscuss mediators of UCP3 regulation and propose a potential role for intracellular fatty acidsin the mechanism of UCP3 modulation. Finally, we hypothesize a role for UCP3 in themetabolic adaptation of the mitochondria to the degradation of fatty acids.  相似文献   

14.
Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. CHANGE was a randomized, parallel‐group, superiority, multi‐centre trial with blinded outcome assessment, testing the efficacy of an intervention aimed to improve cardiovascular risk profile and hereby potentially reduce mortality. A total of 428 patients with schizophrenia spectrum disorders and abdominal obesity were recruited and centrally randomized 1:1:1 to 12 months of lifestyle coaching plus care coordination plus treatment as usual (N=138), or care coordination plus treatment as usual (N=142), or treatment as usual alone (N=148). The primary outcome was 10‐year risk of cardiovascular disease assessed post‐treatment and standardized to age 60. At follow‐up, the mean 10‐year risk of cardiovascular disease was 8.4 ± 6.7% in the group receiving lifestyle coaching, 8.5 ± 7.5% in the care coordination group, and 8.0 ± 6.5% in the treatment as usual group (p=0.41). We found no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, physical activity, weight, diet and smoking. In conclusion, the CHANGE trial did not support superiority of individual lifestyle coaching or care coordination compared to treatment as usual in reducing cardiovascular risk in patients with schizophrenia spectrum disorders and abdominal obesity.  相似文献   

15.
Associations of parity with body fat and its distribution are poorly understood; therefore, we examined the relationships between parity and obesity in young adult women. Body mass index (BMI), skin folds, and waist-hip ratio were compared in 1452 African-American and 1268 Caucasian nonpregnant women aged 18 to 30, adjusting for age (where no age-parity interactions were present), education, physical activity (assessed by questionnaire) and fitness (assessed by graded exercise test), dietary fat intake, alcohol and smoking. Adjusted mean BMI was significantly higher in African-American women aged 25–30 years with three or more children (28.5 kg/m2) than in those with two (27.0 kg/m2), one (26.2 kg/m2), or no children (26.3 kg/m2). Similar trends were found in Caucasians (BMI = 23.3, 23.4, 23.7, 25.0 kg/m2 for parity = 0,1, 2, ≥ 3, respectively), but the mean BMI was significantly higher in African Americans in each parity group. The association between BMI and parity was not present among women 18–24 years of age. Skinfolds were directly associated with parity in African Americans only. Waist-hip ratios were generally lower among nulliparous than parous women in both ethnic groups; race differences were present only among nulliparas. In conclusion, parity was associated with BMI in women aged 25 to 30 years but did not explain ethnicity-related differences in body mass.  相似文献   

16.
Adult adipose tissue contains a large supply of progenitors that can renew fat cells for homeostatic tissue maintenance and adaptive growth or regeneration in response to external challenges. However, the in vivo mechanisms that control adipocyte progenitor behavior are poorly characterized. We recently demonstrated that recruitment of adipocyte progenitors by macrophages is a central feature of adipose tissue remodeling under various adipogenic conditions. Catabolic remodeling of white adipose tissue by β3-adrenergic receptor stimulation requires anti-inflammatory M2-polarized macrophages to clear dying adipocytes and to recruit new brown adipocytes from progenitors. In this Extra Views article, we discuss in greater detail the cellular elements of adipogenic niches and report a strategy to isolate and characterize the subpopulations of macrophages and adipocyte progenitors that actively participate in adrenergic tissue remodeling. Further characterization of these subpopulations may facilitate identification of new cellular targets to improve metabolic and immune function of adipose tissue.  相似文献   

17.
18.
Adán  C.  Grasa  M.M.  Cabot  C.  Esteve  M.  Vilà  R.  Masanés  R.  Estruch  J.  Fernández-López  J.A.  Remesar  X.  Alemany  M. 《Molecular and cellular biochemistry》1999,197(1-2):109-115
Young female Zucker fa/fa rats of 370-430 g were implanted with osmotic minipumps releasing 3.5 mol/dayúkg of estrone oleate in liposomes (Merlin-2) into the bloodstream for up to 14 days. Merlin-2 induced a sustained loss of appetite, and a decrease in body weight of 3.5%, which contrasts with the 8.2% increase in controls during the period studied. Plasma insulin, glucose and urea decreased, and liver glycogen increased with Merlin-2 treatment. Plasma ACTH and corticosterone increased to a maximum at the end of the experiment. The expression of the ob gene in adipose tissue was unchanged, and plasma leptin levels were also unchanged by treatment. Estrone levels increased more than 1500-fold, and estrone oleate rose 100-fold during treatment. The fact that estrone oleate had no effect on the leptin levels or expression in obese rats, in contrast with the marked inhibition observed in the lean suggests that the functionality of the leptin receptor is essential for estrone oleate inhibition of the ob gene. This also suggests that leptin may control ob gene expression in white adipose tissue and that estrone oleate may activate this process. The slimming effect of estrone oleate is, thus, not directly dependent on leptin, since both normoleptinemic and hyperleptinemic animals lose fat following treatment nor are the effects on appetite and energy expenditure mediated by leptin. However, leptin levels and the expression of the ob gene are directly linked with estrone oleate function. A possible involvement of leptin in estrone oleate action is postulated. The results support the participation of estrone oleate in the control of body weight and hint at the complexity of its regulation by leptin and glucocorticoids.  相似文献   

19.
《Cytotherapy》2014,16(2):245-257
Background aimsNon-revascularizable critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease, with no therapeutic option. Extensive preclinical studies have demonstrated that adipose-derived stroma cell (ASC) transplantation strongly improves revascularization and tissue perfusion in ischemic limbs. This study, named ACellDREAM, is the first phase I trial to evaluate the feasibility and safety of intramuscular injections of autologous ASC in non-revascularizable CLI patients.MethodsSeven patients were consecutively enrolled, on the basis of the following criteria: (i) lower-limb rest pain or ulcer; (ii) ankle systolic oxygen pressure <50 or 70 mm Hg for non-diabetic and diabetic patients, respectively, or first-toe systolic oxygen pressure <30 mm Hg or 50 mm Hg for non-diabetic and diabetic patients, respectively; (iii) not suitable for revascularization. ASCs from abdominal fat were grown for 2 weeks and were then characterized.ResultsMore than 200 million cells were obtained, with almost total homogeneity and no karyotype abnormality. The expressions of stemness markers Oct4 and Nanog were very low, whereas expression of telomerase was undetectable in human ASCs compared with human embryonic stem cells. ASCs (108) were then intramuscularly injected into the ischemic leg of patients, with no complication, as judged by an independent committee. Trans-cutaneous oxygen pressure tended to increase in most patients. Ulcer evolution and wound healing showed improvement.ConclusionsThese data demonstrate the feasibility and safety of autologous ASC transplantation in patients with objectively proven CLI not suitable for revascularization. The improved wound healing also supports a putative functional efficiency.  相似文献   

20.
Apolipoprotein (apo) C-III is a marker protein of triacylglycerol (TG)-rich lipoproteins and high-density lipoproteins (HDL), and has been proposed as a risk factor of coronary heart disease. To compare the physiologic role of reconstituted HDL (rHDL) with or without apoC-III, we synthesized rHDL with molar ratios of apoA-I:apoC-III of 1:0, 1:0.5, 1:1, and 1:2. Increasing the apoC-III content in rHDL produced smaller rHDL particles with a lower number of apoA-I molecules. Furthermore, increasing the molar ratio of apoC-III in rHDL enhanced the surfactant-like properties and the ability to lyse dimyristoyl phosphatidylcholine. Furthermore, rHDL containing apoC-III was found to be more resistant to particle rearrangement in the presence of low-density lipoprotein (LDL) than rHDL that contained apoA-I alone. In addition, the lecithin:cholesterol acyltransferase (LCAT) activation ability was reduced as the apoC-III content of the rHDL increased; however, the CE transfer ability was not decreased by the increase of apoC-III. Finally, rHDL containing apoC-III aggravated the production of MDA in cell culture media, which led to increased cellular uptake of LDL. Thus, the addition of apoC-III to rHDL induced changes in the structural and functional properties of the rHDL, especially in particle size and rearrangement and LCAT activation. These alterations may lead to beneficial functions of HDL, which is involved in anti-atherogenic properties in the circulation.  相似文献   

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