共查询到20条相似文献，搜索用时 15 毫秒
1.
Rat liver mitochondria, in different steps of the maturation process, were resolved by differential centrifugation at 1000g (M1), 3000g (M3), and 10,000g (M10), and their characteristics determining susceptibility to stress conditions were investigated. Some parameters did not show gradual changes in the transition from M10 to M1 fraction because of the contamination of the M10 fraction by microsomes and damaged mitochondria with relatively high lipid content. The highest and lowest rates of O2 consumption and H2O2 production were exhibited by M1 and M10 fractions, respectively. Vitamin E and coenzyme Q levels were significantly higher in M10 than in M1 fraction, whereas whole antioxidant capacity was not significantly different. The degree of oxidative damage to lipids and proteins was higher in M1 and not significantly different in M3 and M10 fractions. The order of susceptibility to both oxidative challenge and Ca2+-induced swelling was M1 > M3 > M10. It seems that the Ca2+-induced swelling is due to permeabilization of oxidatively altered inner membrane and leads to discard mitochondria with high ROS production. If, as previous reports suggest, mitochondrial damage is initiating stimulus to mitochondrial biogenesis, the susceptibility of the M1 mitochondria to stressful conditions could be important to regulate cellular ROS production. In fact, it should favor the substitution of the oldest ROS-overproducing mitochondria with neoformed mitochondria endowed with a smaller capacity to produce free radicals. 相似文献
2.
Accelerated glucose metabolism leads to oxidative stress and DNA damage in cells; these effects are related to glucose toxicity. The precise mechanisms of glucose toxicity are still unclear. The aim of this work was to investigate the mechanism of poly(ADP‐ribose) polymerase 1 (PARP1), which is a DNA repair enzyme activated by high‐glucose‐induced oxidative stress, and its effect on glucose toxicity in HepG2 hepatocytes. HepG2 cells were cultured under normal (5.5 mM) or high (30 mM) glucose conditions for 4 days. PJ34, which is an inhibitor of PARP1, was used to determine the downstream effects of PARP1 activation. PARP1 activity in 30 mM‐glucose‐treated cells was more than that in 5.5 mM‐glucose‐treated cells, and the activity correlated with the increase in ROS generation and DNA damage. PJ34 suppressed PARP1 activation and prevented the high‐glucose‐induced suppression of SIRT1 and AMP‐activated protein kinase (AMPK) activity, which was similar to its effect on the restoration of intracellular nicotinamide adenine dinucleotide (NAD) content. Further, the phosphorylation of insulin receptor was attenuated in response to insulin stimulation under high glucose conditions, and PJ34 could reverse this effect. The results of transfection of HepG2 cells with PARP1 small interfering RNA were similar to those obtained by treatment of the cells with PARP1 inhibitor PJ34. These data suggest that high‐glucose‐induced PARP1 activation might play a role in glucose toxicity by down‐regulating SIRT1 and AMPK activity through NAD depletion and resulting in insulin insensitivity. J. Cell. Biochem. 112: 299–306, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
3.
Justo Sierra‐Johnson Bruce D. Johnson Kent R. Bailey Stephen T. Turner 《Obesity (Silver Spring, Md.)》2004,12(12):2070-2077
Objective: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (SI) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist‐to‐hip ratio (WHR). Research Methods and Procedures: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non‐Hispanic white subjects from Rochester, MN (age 19‐60 years; 123 men and 133 women) to determine the SI index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with SI after sex stratification and adjustment for age. Results: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in SI among women than among men. In men, after controlling for age, all of the predictive information of SI was provided by waist circumference (additional R2 = 0.39, p < 0.001); none of the DXA measures improved the ability to predict SI. In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of SI was percentage head fat (additional R2 = 0.03, p < 0.001). Discussion: Equivalent increases in most measures of body fat had lesser impact on SI in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures. 相似文献
4.
Terry T.-K. Huang Maria S. Johnson Barbara A. Gower Michael I. Goran Ph.D. 《Obesity (Silver Spring, Md.)》2002,10(10):978-984
Objective: To develop mixed models for examining longitudinal associations between rates of change in visceral, subcutaneous abdominal, and total body fat with rates of change in fasting insulin (FI) and insulin sensitivity (SI) over 3 years in children. Research Methods and Procedures: Seventy-seven children (mean age, 8.3 years at baseline) from Birmingham, Alabama, with three or more annual measures of FI and SI were included. Abdominal fat was measured by computed tomography, and total body fat and lean tissue mass were measured by DXA. Mixed models examined the longitudinal associations between the baseline level/rate of change of different fat compartments and the rate of change in FI or SI. Results: An annual increase of ∼5% in FI was associated with 1 cm2/yr of visceral fat gain per year (p < 0.05), independent of subcutaneous abdominal fat. A 1-cm2 difference in initial subcutaneous abdominal fat was associated with an ∼0.2% increase per year in FI (p < 0.02), independent of visceral fat. None of the rates of change in any of the fat measures was associated with the rate of change of SI. Discussion: The rate of change in visceral fat was positively associated with the rate of change in FI, independent of increasing subcutaneous abdominal fat; however, subcutaneous abdominal fat may be more predictive of the rate of change of FI than visceral or total fat. Therefore, growth-related increases in abdominal fat, particularly subcutaneous abdominal fat, may contribute to accelerating increases in FI, but have no effect on SI. 相似文献
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Objective: To determine the effects of weight loss (WL) alone and combined with aerobic exercise on visceral adipose tissue (VAT), intramuscular fat, insulin‐stimulated glucose uptake, and the rate of decline in free fatty acid (FFA) concentrations during hyperinsulinemia. Research Methods and Procedures: We studied 33 sedentary, obese (BMI = 32 ± 1 kg/m2) postmenopausal women who completed a 6‐month (three times per week) program of either WL alone (n = 16) or WL + aerobic exercise (AEX) (n = 17). Glucose utilization (M) was measured during a 3‐hour hyperinsulinemic‐euglycemic clamp (40 mU/m2 per minute). M/I, the amount of glucose metabolized per unit of plasma insulin (I), was used as an index of insulin sensitivity. Results: Body weight, total fat mass, and percentage fat decreased similarly in both groups (p < 0.01). VAT, subcutaneous abdominal adipose tissue, mid‐thigh subcutaneous fat, and intramuscular fat decreased to a similar extent in both groups and between 14% and 27% after WL and WL+AEX (p < 0.05). WL alone did not change M or M/I; however, M and M/I increased 15% and 21% after WL+AEX (p < 0.05). Fasting concentrations and rate of decline of FFA did not change in either group. In stepwise regression models to determine the independent predictors of changes in M and M/I, the change in VAT was the single independent predictor of M (r2 = 0.30) and M/I (r2 = 0.33). Discussion: Intramuscular fat decreases similarly with 6 months of moderate WL alone or with aerobic exercise in postmenopausal women. In contrast, only WL combined with exercise results in increased glucose utilization and insulin sensitivity. These findings should be validated in a larger population. 相似文献
6.
Sharon J. Marks Niall R. Moore Mo L. Clark Boyd JG Strauss T. Derek R. Hockaday 《Obesity (Silver Spring, Md.)》1996,4(1):1-7
Increased visceral adipose tissue is thought to contribute to impaired glucose tolerance. We studied 10 men with non-insulin dependent diabetes (NIDDM) before and after a 12-week intervention study using dexfenfluramine. Subjects had a mean body mass index (BMI) of 26.4 ± 1.7 kgm2 and had an abdominal distribution of body fatness (waist-to hip ratio >0.9). Anthropometric indices, biochemistry, macronutrient intake from 7-day food records as well as a euglycaemic glucose clamp and magnetic resonance imaging (MRI) were performed at week 0 and week 12. Abdominal adipose tissue area measured by MRI was reduced from 854 ± 270 cm2 to 666 ± 231 cm2 (p=0.003) due mainly to a selective 32% reduction in visceral fat area from 484 ± 230 cm2 to 333 ± 72 cm2 (p=0.002). Insulin sensitivity improved from 0.29 ± 0.13 [min?1 (mU/L)] to 0.54 ± 0.21 [min?1 (mU/L)] (p=0.01) and C-peptide levels reduced from 0.77 ± 0.24 μmol/L to 0.58 ± 0.15 μmol/L (p=0.002). The reductions in fasting glucose and glycated haemoglobin failed to achieve significance. Fasting total cholesterol and triglyceride levels significantly reduced (p=<0.001 and p=0.021 respectively). There was a reduction in total energy intake (p=0.005) due to a significant reduction in calories obtained from fat (p<0.001). Thus dexfenfluramine was shown to be a useful adjunct therapy for the reduction of visceral fat in abdominally-obese men with NIDDM with an associated improvement in insulin sensitivity. 相似文献
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Objective: To determine whether prior eating behavior characterized by dietary restraint alters responses in energy expenditure and substrate oxidation associated with a short‐term, energy‐restricted diet. Research Methods and Procedures: A repeated‐measures, 3‐day diet‐intervention study of adequate (125 kJ/kg of body weight) or restricted (62.5 kJ/kg) energy intake was conducted with 30 women, 20 to 46 years, BMI 25 to 45 kg/m2, whose prior eating behavior was “restrained” or “unrestrained.” The Eating Inventory (cognitive restraint subscale) was used to measure restrained eating behavior. Energy expenditure and substrate oxidation were measured after a 12‐hour fast and during the first and fourth hours after a standard meal. Plasma glucose, nonesterified fatty acids, and insulin were measured at corresponding times. Body composition was determined by total body electrical conductivity. Results: Resting energy expenditure was not affected by 3 days of energy restriction. Short‐term energy restriction resulted in lower respiratory‐exchange ratios, higher rates of fat oxidation, and lower rates of carbohydrate oxidation. Subjects classified as restrained eaters had higher postprandial respiratory‐exchange ratios and carbohydrate‐oxidation rates compared with unrestrained eaters. Fasting insulin concentrations were lower in restrained eaters. These effects associated with prior eating behavior were independent of the diet intervention. Discussion: Metabolic outcomes associated with a 3‐day energy‐restricted diet (i.e., increased fat oxidation and decreased carbohydrate oxidation) were not affected by prior restrained eating behavior. However, restrained eating behavior was associated with increased carbohydrate oxidation after a mixed meal. This effect of restrained eating behavior may be attributable to increased insulin sensitivity. 相似文献
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Objective: Moderate and high alcohol intake have been associated with decreased and increased risk of type 2 diabetes, respectively. Insulin resistance, insulin secretion, and abdominal obesity are major predictors of diabetes, but the links with alcohol intake remain contradictory because of limited data. Research Methods and Procedures: In a population‐based cohort of 807 men (age, 70 years), we studied whether alcohol intake was related to insulin sensitivity, measured with the gold standard technique (euglycemic clamp), insulin secretion (early insulin response), or adiposity [BMI, waist circumference (WC), waist‐to‐hip ratio]. Alcohol intake was self‐reported (questionnaire) and was assessed from a validated 7‐day dietary record. The cross‐sectional associations were evaluated using multivariable linear regression, adjusting for smoking, education level, physical activity, dietary total energy intake, hypertension, diabetes, triglycerides, and cholesterol. Results: In multivariable models, self‐estimated alcohol intake was not related to insulin sensitivity, early insulin response, or BMI, but was positively related to WC (β‐coefficient, 0.77; 95% confidence interval, 0.15 to 1.39; p = 0.02) and waist‐to‐hip ratio (0.006 [0.002–0.009], p = 0.003). The association with WC and waist‐to‐hip ratio was most pronounced in men in the lowest tertile of BMI. The results using dietary records were similar. Discussion: Evaluated in a large sample in elderly men, neither insulin sensitivity measured by clamp technique nor insulin secretion was significantly associated with alcohol intake. However, high alcohol intake was associated with abdominal obesity, which might explain the higher diabetes risk previously observed in high alcohol consumers. 相似文献
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Marc J. Weigensberg Geoff D.C. Ball Gabriel Q. Shaibi Martha L. Cruz Barbara A. Gower Michael I. Goran 《Obesity (Silver Spring, Md.)》2005,13(9):1630-1637
Objective: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. Research Methods and Procedures: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24‐hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above‐AMDR/within‐AMDR guidelines), and differences were analyzed by 2 × 2 analysis of covariance, adjusting for covariates. Results: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above‐AMDR compared with within‐AMDR blacks) and was not seen in whites. Discussion: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation. 相似文献
11.
Alessandra Nunes Faria Fernando Flexa Ribeiro Filho Sandra Roberta Gouveia Ferreira Maria Teresa Zanella 《Obesity (Silver Spring, Md.)》2002,10(12):1203-1206
Objective: The relationship among body fat distribution, blood pressure, serum leptin levels, and insulin resistance was investigated in hypertensive obese women with central distribution of fat. Research Methods and Procedures: We studied 74 hypertensive women (age, 49.8 ± 7.5 years; body mass index, 39.1 ± 5.5 kg/m2; waist-to-hip ratio, 0.96 ± 0.08). All patients were submitted to 24-hour blood pressure ambulatory monitoring (24h-ABPM). Abdominal ultrasonography was used to estimate the amount of visceral fat (VF). Fasting blood samples were obtained for serum leptin and insulin determinations. Insulin resistance was estimated by homeostasis model assessment insulin resistance index (HOMA-r index). Results: Sixty-four percent of the women were postmenopausal, and all patients showed central distribution of fat (waist-to-hip ratio > 0.85). The VF correlated with systolic 24h-ABPM values (r = 0.28, p = 0.01) and with HOMA-r index (r = 0.27; p = 0.01). VF measurement (7.5 ± 2.3 vs. 5.9 ± 2.2 cm, p < 0.001) and the systolic 24h-ABPM (133 ± 14.5 vs. 126 ± 9.8 mm Hg, p = 0.04), but not HOMA-r index, were significantly higher in the postmenopausal group (n = 48) than in the premenopausal group (n = 26). No correlations were observed between blood pressure levels and HOMA-r index, leptin, or insulin levels. In the multiple regression analysis, visceral fat, but not age, body fat mass, or HOMA-r index, correlated with the 24h-ABPM (p = 0.003). Discussion: In centrally obese hypertensive women, the accumulation of VF, more often after menopause, is associated with higher levels of blood pressure and insulin resistance. The mechanism through which VF contributes to higher blood pressure levels seems to be independent of leptin or insulin levels. 相似文献
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Magdalene K. Montgomery Brenna Osborne Simon H. J. Brown Lewin Small Todd W. Mitchell Gregory J. Cooney Nigel Turner 《Journal of lipid research》2013,54(12):3322-3333
Dietary intake of long-chain fatty acids (LCFAs) plays a causative role in insulin resistance and risk of diabetes. Whereas LCFAs promote lipid accumulation and insulin resistance, diets rich in medium-chain fatty acids (MCFAs) have been associated with increased oxidative metabolism and reduced adiposity, with few deleterious effects on insulin action. The molecular mechanisms underlying these differences between dietary fat subtypes are poorly understood. To investigate this further, we treated C2C12 myotubes with various LCFAs (16:0, 18:1n9, and 18:2n6) and MCFAs (10:0 and 12:0), as well as fed mice diets rich in LCFAs or MCFAs, and investigated fatty acid-induced changes in mitochondrial metabolism and oxidative stress. MCFA-treated cells displayed less lipid accumulation, increased mitochondrial oxidative capacity, and less oxidative stress than LCFA-treated cells. These changes were associated with improved insulin action in MCFA-treated myotubes. MCFA-fed mice exhibited increased energy expenditure, reduced adiposity, and better glucose tolerance compared with LCFA-fed mice. Dietary MCFAs increased respiration in isolated mitochondria, with a simultaneous reduction in reactive oxygen species generation, and subsequently low oxidative damage. Collectively our findings indicate that in contrast to LCFAs, MCFAs increase the intrinsic respiratory capacity of mitochondria without increasing oxidative stress. These effects potentially contribute to the beneficial metabolic actions of dietary MCFAs. 相似文献
13.
《Free radical research》2013,47(8):935-945
AbstractOxidative stress and mitochondrial dysfunction are hypothesized to contribute to the pathogenesis of chronic cholestatic liver diseases. Silent information regulator 1 (SIRT1) attenuates oxidative stress and improves mitochondrial biogenesis in numerous mitochondrial-related diseases; however, a functional role for SIRT1 in chronic liver cholestasis, characterized by increased levels of toxic bile acids, remains unknown. We show decrease in SIRT1 levels and its activity and impairment of mitochondrial biogenesis in the liver of patients with extrahepatic cholestasis. Moreover, we found that glycochenodeoxycholic acid (GCDCA) stimulated cytotoxicity, disrupted the mitochondrial membrane potential, increased reactive oxygen species production, and decreased mitochondrial mass and mitochondrial DNA content in L02 cells. Consistent with this finding, GCDCA was found to decrease SIRT1 protein expression and activity, thus promoting the deacetylation of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α), a key enzyme involved in mitochondrial biogenesis and function. Conversely, GCDCA-induced mitochondrial injury was efficiently attenuated by SIRT1 overexpression. In summary, these findings indicate that the loss of SIRT1 may play a crucial role in the pathogenesis of liver damage observed in patients with extrahepatic cholestasis. The findings also indicate that genetic supplementation of SIRT1 can ameliorate GCDCA-induced hepatotoxicity through the activation of PGC-1α-dependent mitochondrial biogenesis. 相似文献
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Zhongchi Li Kang Xu Yannan Guo Lu Ping Yuqi Gao Ying Qiu Jianquan Ni Qingfei Liu Zhao Wang 《Aging cell》2020,19(3)
Mammalian sirtuin 6 (SIRT6) is involved in the regulation of many essential processes, especially metabolic homeostasis. SIRT6 knockout mice undergo premature aging and die at age ~4 weeks. Severe glycometabolic disorders have been found in SIRT6 knockout mice, and whether a dietary intervention can rescue SIRT6 knockout mice remains unknown. In our study, we found that at the same calorie intake, a high‐fat diet dramatically increased the lifespan of SIRT6 knockout mice to 26 weeks (males) and 37 weeks (females), reversed multi‐organ atrophy, and reduced body weight, hypoglycemia, and premature aging. Furthermore, the high‐fat diet partially but significantly normalized the global gene expression profile in SIRT6 knockout mice. Regarding the mechanism, excessive glucose uptake and glycolysis induced by the SIRT6 deficiency were attenuated in skeletal muscle through inhibition of insulin and IGF1 signaling by the high‐fat diet. Similarly, fatty acids but not ketone bodies inhibited glucose uptake, glycolysis, and senescence in SIRT6 knockout fibroblasts, whereas PI3K inhibition antagonized the effects of a high‐fatty‐acid medium in vitro. Overall, the high‐fat diet dramatically reverses numerous consequences of SIRT6 deficiency through modulation of insulin and IGF1 signaling, providing a new basis for elucidation of SIRT6 and fatty‐acid functions and supporting novel therapeutic approaches against metabolic disorders and aging‐related diseases. 相似文献
15.
Cheng Lu Bing Jiang Jie Xu Xuan Zhang Nianxin Jiang 《Journal of biochemical and molecular toxicology》2023,37(8):e23398
Acute myocardial infarction is regarded as myocardial necrosis resulting from myocardial ischemia/reperfusion (I/R) damage and retains a major cause of mortality. Neferine, which was extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., has been reported to possess a broad range of biological activities. However, its underlying mechanism on the protective effect of I/R has not been fully clarified. A hypoxia/reoxygenation (H/R) model with H9c2 cells closely simulating myocardial I/R injury was used as a cellular model. This study intended to research the effects and mechanism underlying neferine on H9c2 cells in response to H/R stimulation. Cell Counting Kit-8 and lactate dehydrogenase (LDH) release assays were employed to measure cell viability and LDH, respectively. Apoptosis and reactive oxygen species (ROS) were determined by flow cytometry analysis. Oxidative stress was evaluated by detecting malondialdehyde, superoxide dismutase, and catalase. Mitochondrial function was assessed by mitochondrial membrane potential, ATP content, and mitochondrial ROS. Western blot analysis was performed to examine the expression of related proteins. The results showed that hypoxia/reoxygenation (H/R)-induced cell damage, all of which were distinctly reversed by neferine. Moreover, we observed that neferine inhibited oxidative stress and mitochondrial dysfunction induced by H/R in H9c2 that were concomitant with increased sirtuin-1 (SITR1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 expression. On the contrary, silencing the SIRT1 gene with its small interferingRNA eliminated the beneficial effects of neferine. It is concluded that neferine preconditioning attenuated H/R-induced cardiac damage via suppressing apoptosis, oxidative stress, and mitochondrial dysfunction, which may be partially ascribed to the activation of SIRT1/Nrf2 signaling pathway. 相似文献
16.
Objective: In healthy lean individuals, changes in insulin sensitivity occurring as a consequence of a 2‐day dexamethasone administration are compensated for by changes in insulin secretion, allowing glucose homeostasis to be maintained. This study evaluated the changes in glucose metabolism and insulin secretion induced by short‐term dexamethasone administration in obese women. Research Methods and Procedures: Eleven obese women with normal glucose tolerance were studied on two occasions, without and after 2 days of low‐dose dexamethasone administration. A two‐step hyperglycemic clamp (7.5 and 10 mM glucose) with 6, 6 2H2 glucose was used to assess insulin secretion and whole body glucose metabolism. Results were compared with those obtained in a group of eight lean women. Results: Without dexamethasone, obese women had higher plasma insulin concentrations in the fasting state, during the first phase of insulin secretion, and at the two hyperglycemic plateaus. However, they had normal whole body glucose metabolism compared with lean women, indicating adequate compensation. After dexamethasone, obese women had a 66% to 92% increase in plasma insulin concentrations but a 15.4% decrease in whole body glucose disposal. This contrasted with lean women, who had a 91% to 113% increase in plasma insulin concentrations, with no change in whole body glucose disposal. Discussion: Dexamethasone administration led to a significant reduction in whole body glucose disposal at fixed glycemia in obese but not lean women. This indicates that obese women are unable to increase their insulin secretion appropriately. 相似文献
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Yahong Cheng;Puxin Huang;Qixian Zou;Hui Tian;Qingzhou Cheng;Hong Ding; 《Journal of neurochemistry》2024,168(12):3962-3981
Both human and animal experiments have demonstrated that energy metabolism dysfunction in neurons after seizures is associated with an imbalance in mitochondrial fusion/fission dynamics. Effective neuronal mitochondrial dynamics regulation strategies remain elusive. Nicotinamide mononucleotide (NMN) can ameliorate mitochondrial functional and oxidative stress in age-related diseases. But whether NMN improves mitochondrial energy metabolism to exert anti-epileptic effects is unclear. This study aims to clarify if NMN can protect neurons from pentylenetetrazole (PTZ) or Mg2+-free-induced mitochondrial disorder and apoptosis via animal and cell models. We established a continuous 30-day PTZ (37 mg/kg) intraperitoneal injection-induced epileptic mouse model and a cell model induced by Mg2+-free solution incubation to explore the neuroprotective effects of NMN. We found that NMN treatment significantly reduced the seizure intensity of PTZ-induced epileptic mice, improved their learning and memory ability, and enhanced their motor activity and exploration desire. At the same time, in vitro and in vivo experiments showed that NMN can inhibit neuronal apoptosis and improve the mitochondrial energy metabolism function of neurons. In addition, NMN down-regulated the expression of mitochondrial fission proteins (Drp1 and Fis1) and promoted the expression of mitochondrial fusion proteins (Mfn1 and Mfn2) by activating the SIRT1-PGC-1α pathway, thereby inhibiting PTZ or Mg2+-free extracellular solution-induced mitochondrial dysfunction, cell apoptosis, and oxidative stress. However, combined intervention of SIRT1 inhibitor, Selisistat, and PGC-1α inhibitor, SR-18292, eliminated the regulatory effect of NMN pre-treatment on mitochondrial fusion and fission proteins and apoptosis-related proteins. Therefore, NMN intervention may be a new potential treatment for cognitive impairment and behavioral disorders induced by epilepsy, and targeting the SIRT1-PGC-1α pathway may be a promising therapeutic strategy for seizures. 相似文献
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目的:观察剧烈运动导致的胰岛素敏感性改变及其氧化应激因素。方法:健康青年人服用维生素C和芦丁后作5km/20min越野运动,测试运动前后血清SOD-1、血糖、血清胰岛素、胰岛素敏感性指数,与不服用药物运动前后以上指标相对照。结果:运动后血糖无明显变化,血清胰岛素升高(P<0.01),血清SOD-1及胰岛素敏感指数较之运动前下降(P<0.01);服用药物者在运动后血清SOD-1及胰岛素敏感性指数较不服用药物者升高(P<0.05)。结论:剧烈运动后短时间内胰岛素敏感性下降,运动中过度氧化是胰岛素敏感性下降重要原因。 相似文献
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