scholarly journals Moderation of mitochondrial respiration mitigates metabolic syndrome of aging

2020 ◽  
Vol 117 (18) ◽  
pp. 9840-9850 ◽  
Author(s):  
Mojdeh Tavallaie ◽  
Ramouna Voshtani ◽  
Xinxian Deng ◽  
Yixue Qiao ◽  
Faqin Jiang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mitochondrial Respiration ◽  
Mitochondrial Dynamics ◽  
Atp Synthesis ◽  
Control Group ◽  
Standard Diet ◽  
Ros Production ◽  
Metabolic Complications ◽  
Age Related ◽  
Mitochondrial Functions

Deregulation of mitochondrial dynamics leads to the accumulation of oxidative stress and unhealthy mitochondria; consequently, this accumulation contributes to premature aging and alterations in mitochondria linked to metabolic complications. We postulate that restrained mitochondrial ATP synthesis might alleviate age-associated disorders and extend healthspan in mammals. Herein, we prepared a previously discovered mitochondrial complex IV moderate inhibitor in drinking water and orally administered to standard-diet-fed, wild-type C57BL/6J mice every day for up to 16 mo. No manifestation of any apparent toxicity or deleterious effect on studied mouse models was observed. The impacts of an added inhibitor on a variety of mitochondrial functions were analyzed, such as respiratory activity, mitochondrial bioenergetics, and biogenesis, and a few age-associated comorbidities, including reactive oxygen species (ROS) production, glucose abnormalities, and obesity in mice. It was found that mitochondrial quality, dynamics, and oxidative metabolism were greatly improved, resulting in lean mice with a specific reduction in visceral fat plus superb energy and glucose homeostasis during their aging period compared to the control group. These results strongly suggest that a mild interference in ATP synthesis through moderation of mitochondrial activity could effectively up-regulate mitogenesis, reduce ROS production, and preserve mitochondrial integrity, thereby impeding the onset of metabolic syndrome. We conclude that this inhibitory intervention in mitochondrial respiration rectified the age-related physiological breakdown in mice by protecting mitochondrial function and markedly mitigated certain undesired primary outcomes of metabolic syndrome, such as obesity and type 2 diabetes. This intervention warrants further research on the treatment of metabolic syndrome of aging in humans.

scholarly journals Mitochondrial Respiration in KRAS and BRAF Mutated Colorectal Tumors and Polyps

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 815 ◽  
Author(s):  
Egle Rebane-Klemm ◽  
Laura Truu ◽  
Leenu Reinsalu ◽  
Marju Puurand ◽  
Igor Shevchuk ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Atp Synthesis ◽  
Colorectal Polyps ◽  
Metabolic Phenotype ◽  
Mitochondrial Outer Membrane ◽  
Control Group ◽  
Colon Polyps ◽  
Wild Type ◽  
Tissue Samples ◽  
Potential Component

This study aimed to characterize the ATP-synthesis by oxidative phosphorylation in colorectal cancer (CRC) and premalignant colon polyps in relation to molecular biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected. Patients with polyps and CRC were divided into three molecular groups: KRAS mutated, BRAF mutated and KRAS/BRAF wild-type. Mitochondrial respiration in permeabilized tissue samples was observed using high resolution respirometry. ADP-activated respiration rate (Vmax) and an apparent affinity of mitochondria to ADP, which is related to mitochondrial outer membrane (MOM) permeability, were determined. Clear differences were present between molecular groups. KRAS mutated CRC group had lower Vmax values compared to wild-type; however, the Vmax value was higher than in the control group, while MOM permeability did not change. This suggests that KRAS mutation status might be involved in acquiring oxidative phenotype. KRAS mutated polyps had higher Vmax values and elevated MOM permeability as compared to the control. BRAF mutated CRC and polyps had reduced respiration and altered MOM permeability, indicating a glycolytic phenotype. To conclude, prognostic biomarkers KRAS and BRAF are likely related to the metabolic phenotype in CRC and polyps. Assessment of the tumor mitochondrial ATP synthesis could be a potential component of patient risk stratification.

scholarly journals Effects of different exercise loads on serum betatrophin (ANGPTL-8/lipasin) and cartonectin (CTRP-3) levels in metabolic syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Muhammed Emre Karaman ◽  
Cengiz Arslan ◽  
Mehmet Ferit Gürsu
Keyword(s):  
Metabolic Syndrome ◽  
Aerobic Exercise ◽  
Tap Water ◽  
Exercise Group ◽  
Anaerobic Exercise ◽  
Male Rats ◽  
Control Group ◽  
Standard Diet ◽  
Positive Effects ◽  
Significant Difference

Abstract Objectives The number of studies examining the circulating level change of betatrophin and cartonectin in metabolic syndrome applying different loads of exercise is limited. The purpose of the present study was to investigate how different loads of exercises regulate the betatrophin and cartonectin levels in metabolic syndrome induced rats. Methods A total of 24 Wistar-Albino male rats were used in the study. Rats were divided into four groups as follows; G1: control group (fed with standard diet and tap water), G2: metabolic syndrome group (without exercise application), G3: metabolic syndrome + aerobic exercise group (aerobic exercise applied), G4: metabolic syndrome + anaerobic exercise group (anaerobic exercise applied). Betatrophin and Cartonectin levels were determined by ELISA method in serum samples. Results There was a statistically significant difference in betatrophin levels between the groups and this differentiation was caused by G2 (p <0.05). Cartonectin levels were not significantly different between groups (p> 0.05). Conclusions It can be concluded that anaerobic exercises have more positive effects on glucose balance in metabolic syndrome than aerobic exercises, and by regulating betatrophin levels, anaerobic exercises indicate this effect.

scholarly journals THE STUDY OF THE SPECIFIC ACTIVITY OF AMITRIPTILIN AND PROFLUZAK ON A MODEL OF INDUCED METABOLIC SYNDROME IN SPONTLY HYPERTENSIVE ANIMALS

2019 ◽  
Vol 6 (1) ◽  
pp. 58-68
Author(s):  
U. P. Uspenskiy ◽  
E. V. Balukova ◽  
V. G. Makarov ◽  
M. N. Makarova ◽  
M. A. Kovaleva
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
Feed Intake ◽  
Specific Activity ◽  
Clinical Manifestations ◽  
Cafeteria Diet ◽  
Behavioral Activity ◽  
Control Group ◽  
Standard Diet ◽  
Intact Group

Background.The direct pathophysiological effects of depression on the components of MS lead to the development of atherosclerosis risk factors. The use of antidepressants minimizes life-threatening clinical manifestations of coronary artery disease and the formation of a pathological stereotype of eating behavior.Objective.To study the specific activity of antidepressants on induced metabolic syndrome in spontaneously hypertensive animals.Design and methods.Work performed on rats (males line SHR). The intact group was on a standard diet, the control group and the groups that received the drugs (amitriptyline and intraludial vaccine, 16.2 mg/kg and 1.7 mg/kg respectively, once a day for five weeks) — on the “cafeteria diet”.Results.With the induction of MS in the groups receiving the diet “cafeteria diet” there was an increase in body weight by 5 % relative to intact animals, fasting glucose levels exceeding 7.2 ± 0.9 mmol/l, a tendency to an increase in serum cholesterol (CS) blood more than 2.0 ± 0.1 mmol/l. Against the background of the use of the studied drugs, there was a statistically significant reduction in feed intake by 77 and 59 % and a decrease in body weight relative to the control group by 10 and 8 % respectively. Significant dynamics of indicators of GTT, cholesterol, TG, LDL and HDL with the use of antidepressants was not observed.Conclusion.A pronounced anti-bulimic effect of the studied drugs, manifested in a decrease in feed intake, a decrease in body weight, was noted. Positive dynamics on carbohydrate and lipid exchanges, indicators of blood pressure, behavioral activity of animals was not observed.

scholarly journals The effects of combined therapy of myo-inositol and D-chiro inositol in reduction of the individual components of metabolic syndrome in overweight PCOS patients compared to myo-inositol supplementation alone: a prospective randomised controlled trial

2017 ◽  
Vol 6 (7) ◽  
pp. 2939 ◽  
Author(s):  
Manideepa Pande ◽  
Ashish Seal ◽  
Sukanta Mishra ◽  
Arup Dasgupta ◽  
Mousumi Sengupta ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Drug Therapy ◽  
Blood Sugar ◽  
Controlled Trial ◽  
Combined Therapy ◽  
Signs And Symptoms ◽  
Reproductive Age ◽  
Fasting Blood Sugar ◽  
Control Group ◽  
Metabolic Complications

Background: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorder affecting five to ten percent women of reproductive age group. Variability of signs and symptoms along with metabolic syndrome as one of the long term complications make it worthy of early diagnosis and treatment. Medical management of PCOS is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularities.Methods: 140 patients, using inclusion and exclusion criteria, were selected and randomly divided into two groups (seventy in each) and age, BMI, waist hip ratio, blood pressure (systolic, diastolic), serum fasting insulin, fasting blood sugar, total cholesterol, HDL, LDL, triglycerides were measured. Study group were given {Myo-inositol (550 mg) + D-chiro-inositol (13.8 mg)} (MI+DCI) twice daily and the control group were given Myo-inositol (1 gm) (MI) twice daily for six months. Same variables were measured at the end of three and six months and compared with repeated measurement ANOVA using SPSS (version 20).Results: Comparison between these two groups before study was non-contributory. Combined drug therapy has provided statistically significant decrease in BMI, W:H ratio, Diastolic BP, Fasting blood sugar at the end of both 3rd and 6th month but in case of LDL it was at the end of 3 months. Combined drug therapy also increased the HDL level significantly in both the occasions.Conclusions: Combined medical therapy by (MI+DCI) is very much helpful in reducing the metabolic complications of PCOS without any major side effects.

scholarly journals eIF5a reduction via decreased Klf5 leads to cell senescence by mitochondrial fission in VSMCs

2019 ◽  
Author(s):  
Dong Ma ◽  
Bin Zheng ◽  
He-liang Liu ◽  
Yong-bo Zhao ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Ros Production ◽  
Ang Ii ◽  
Potential Therapeutic Target ◽  
Cardiovascular Remodeling ◽  
Age Related ◽  
Abdominal Aortic ◽  
Ros Formation ◽  
Vascular Senescence

AbstractThough dysregulation of mitochondrial dynamics has been linked to cellular senescence, which contributes to advanced age-related disorders, it is unclear how Klf5, an essential transcriptional factor of cardiovascular remodeling, mediates the link between mitochondrial dynamics and vascular smooth muscle cell (VSMC) senescence. Here we show that Klf5 downregulation in VSMCs is correlated with rupture of abdominal aortic aneurysm (AAA), an age-related vascular disease. Mice lacking Klf5 in VSMCs exacerbate vascular senescence and progression of Ang II-induced AAA by facilitating ROS formation. Klf5 knockdown enhances, while Klf5 overexpression suppresses mitochondrial fission. Mechanistically, Klf5 activates eIF5a transcription through binding to the promoter of eIF5a, which in turn preserves mitochondrial integrity by interacting with Mfn1. Accordingly, decreased expression of eIF5a elicited by Klf5 downregulation leads to mitochondrial fission and excessive ROS production. Inhibition of mitochondrial fission decreases ROS production and VSMC senescence. Our studies provide a potential therapeutic target for age-related vascular disorders.

scholarly journals Protective Effect of Mitochondrial ND2 C5178A Gene Mutation on Cell and Mitochondrial Functions

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Liuyang Tian ◽  
Chao Zhu ◽  
Huanwan Yang ◽  
Yang Li ◽  
Yuqi Liu
Keyword(s):  
Cell Proliferation ◽  
Gene Mutation ◽  
Atp Synthesis ◽  
Protein Translation ◽  
Control Group ◽  
Protective Effects ◽  
Mitochondrial Oxidative Stress ◽  
Nadh Dehydrogenase Subunit 2 ◽  
Mitochondrial Functions ◽  
Significant Difference

Background. Mitochondrial NADH dehydrogenase subunit 2 (MT-ND2) m. 5178C>A gene mutation has protective effects against various diseases, but the molecular mechanism is still unclear. In previous study, we found a heteroplasmy level of MT-ND2 m. 5178C>A mutation in normotensive controls. Peripheral blood samples were obtained from essential hypertension individuals carrying the mutation and healthy controls without gene mutation to establish immortalized lymphocyte lines. To investigate the effect of the MT-ND2 m. 5178C>A gene mutation, comparative analyses of the two group cell lines were performed, including measurements of cell proliferation, viability, ATP synthesis, mitochondrial oxidative stress, and oxidative phosphorylation. Results. The cell proliferation rate and viability of the MT-ND2 m. 5178C>A mutant lymphocyte line were higher than those of the control group. Mitochondrial functions of the MT-ND2 m. 5178C>A mutant lymphocyte were increased, including increased ATP synthesis, decreased ROS production, increased mitochondrial membrane potential and Bcl-2 gene transcription and protein translation, decreased Caspase 3/7 activity, and decreased early apoptosis and late apoptosis. The oxygen consumption rate (OCR) of the mutant lymphocyte line was higher than that of the control group, including basal OCR, ATP-linked OCR, maximal OCR, proton leak OCR, and reserve OCR, and there was no significant difference in nonmitochondrial OCR. The activity of Mitochondrial Complex I of the mutant group was increased than that of the control group. Conclusions. The MT-ND2 m. 5178C>A mutation is a protective mutation that may be related to improvement of mitochondrial functions and decrease in apoptosis.

scholarly journals Potential Role of Novel Myokine in Rats-Induced Metabolic Syndrome

2021 ◽  
Vol 12 (3) ◽  
pp. 3305-3315
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Potential Role ◽  
Serum Levels ◽  
Treated Group ◽  
Control Group ◽  
Standard Diet ◽  
The Metabolic Syndrome ◽  
Obesity And Diabetes ◽  
Increased Risk

One of the main health problems is metabolic syndrome (MetS). Its incidence elevates with age leading to a higher risk of evolving chronic diseases and cancer. Obesity and insulin resistance was considered the most vital components in its pathogenesis for a long time. This study aims to evaluate serum novel adipokine and myokine to establish the irrelation of insulin resistance and their impact on metabolic syndrome. Four groups of rats were included; the control group (C) fed with a standard diet, the second group (CI) fed on a standard diet and injected daily with irisin (100ng/ ml) till the end of the experiment. The third group (MetS group) fed on the HCHF diet for 20 weeks and served as a control group. Rats in the fourth group (MetS+I group) were fed on the HCHF diet until they become obese and diabetic, then injected daily with irisin (100ng/ ml) till the end of the experiment and served as a treated group. Serum levels of obesity and diabetes indices were significantly increased while HDL was significantly decreased in the metabolic syndrome group, but after treatment with irisin, their levels were improved. Both adropin and irisin were significantly decreased, while IL-6 was significantly increased in the same group that was enhanced after irisin treatment. In conclusion, this study demonstrated that lower irisin correlates with the increased risk of increased risk of insulin resistance and MetS. In addition, our results suggested that irisin could have a potential role in glucose metabolism. The relations among increased levels of circulating irisin, insulin resistance, and MetS prevalence may be elucidated with a physiological compensatory contrivance.

scholarly journals Tomato Powder Modulates NF-κB, mTOR, and Nrf2 Pathways during Aging in Healthy Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kazim Sahin ◽  
Cemal Orhan ◽  
Mehmet Tuzcu ◽  
Hakki Tastan ◽  
Birdal Bilir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Control Group ◽  
Standard Diet ◽  
Glucose And Lipid Metabolism ◽  
Age Related ◽  
Old Rats ◽  
Group 2 ◽  
Tomato Powder ◽  
Group 1

Purpose. In the present study, we aimed to investigate the effects of tomato powder (TP) on glucose and lipid metabolism, as well as oxidative stress and the NF-κB, mTOR, and Nrf2 pathways during the aging process in healthy rats. Methods and Results. Male Wistar rats were randomly assigned to four groups as follows: (i) Control group 1 (n=15, 3-week old): rats were fed standard diet for 7 weeks; (ii) TP group 1 (n=15, 3-week old): rats were fed standard diet supplemented with TP for 7 weeks; (iii) Control group 2 (n=15, 8-week old): rats were fed standard diet for 69 weeks; and (iv) TP group 2 (8-week old): rats were fed standard diet supplemented with TP for 69 weeks. TP supplementation significantly reduced the hyperglycemia, hypertriglyceridemia, and hypercholesterolemia and improved liver function and kidney function in 77-week old rats compared with the control animals (P<0.05). In addition, TP significantly decreased the serum and liver MDA levels (P<0.003 and P<0.001, respectively) while increasing the activities of liver SOD (P<0.001), CAT (P<0.008), and GPx (P<0.01) compared with the control groups in both 10-week-old and 77-week-old rats (P<0.05). Age-related increases in phosphorylation of NF-κBp65, mTOR, 4E-BP1, and P70S6K were observed in livers of 77-week-old rats compared to those of 10-week-old rats (P<0.001). TP supplementation decreased the expression of NF-κBp65 and activation of mTOR, 4E-BP1, and P70S6K in livers of 77-week-old rats compared to the control animals. Moreover, TP supplementation significantly elevated Nrf2 expression in livers of both 10-week-old and 77-week-old rats (P<0.05). Conclusion. TP ameliorates age-associated inflammation and oxidative stress through the inhibition of NF-κBp65, mTOR pathways, and Nrf2 activation may explain the observed improvement in glucose and lipid metabolism as well as the improved liver and kidney functions.

scholarly journals Altered Mitochondrial Respiration and Other Features of Mitochondrial Function inParkin-Mutant Fibroblasts from Parkinson’s Disease Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
William Haylett ◽  
Chrisna Swart ◽  
Francois van der Westhuizen ◽  
Hayley van Dyk ◽  
Lize van der Merwe ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Growth ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Mitochondrial Dynamics ◽  
Dermal Fibroblasts ◽  
Compensatory Mechanism ◽  
Cellular Models ◽  
Mitochondrial Functions

Mutations in theparkingene are the most common cause of early-onset Parkinson’s disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models withparkinnull mutations are particularly valuable for investigating the mitochondrial functions of parkin. However, published results reporting on patient-derivedparkin-mutant fibroblasts have been inconsistent. This study aimed to functionally compareparkin-mutant fibroblasts from PD patients with wild-type control fibroblasts using a variety of assays to gain a better understanding of the role of mitochondrial dysfunction in PD. To this end, dermal fibroblasts were obtained from three PD patients with homozygous whole exon deletions inparkinand three unaffected controls. Assays of mitochondrial respiration, mitochondrial network integrity, mitochondrial membrane potential, and cell growth were performed as informative markers of mitochondrial function. Surprisingly, it was found that mitochondrial respiratory rates were markedly higher in theparkin-mutant fibroblasts compared to control fibroblasts (p= 0.0093), while exhibiting more fragmented mitochondrial networks (p=0.0304). Moreover, cell growth of theparkin-mutant fibroblasts was significantly higher than that of controls (p=0.0001). These unanticipated findings are suggestive of a compensatory mechanism to preserve mitochondrial function and quality control in the absence of parkin in fibroblasts, which warrants further investigation.

scholarly journals Characteristic of Connective Tissue Fibers and Myofibroblasts Interstitium of the Kidneys in Rats Offspring Born to Females with Experimental Metabolic Syndrome

2021 ◽  
Vol 6 (2) ◽  
pp. 37-43
Author(s):  
O. A. Hryhoryeva ◽  
◽  
Ye. V. Korotchuk
Keyword(s):  
Metabolic Syndrome ◽  
Smooth Muscle Actin ◽  
Histochemical Staining ◽  
Collagen Fibers ◽  
Control Group ◽  
Albino Rats ◽  
Standard Diet ◽  
Calorie Diet ◽  
Cortical Substance ◽  
High Calorie

According to a number of studies, it is known that a woman's diet during pregnancy may be one of factors in the violation of nephrogenesis. Obesity in pregnancy may increase markers of fibrosis and the accumulation of extracellular matrix in the kidneys. The purpose of the study is to investigate the dynamics of the content of collagen fibers and myofibroblasts in the cortical and medulla of the kidneys of rat offspring. Materials and methods. The research was based according to the international bioethical regulations, 120 albino rats were involved in the study. The first group is experimental (MC-1): rats born to females with an experimental metabolic syndrome and after the start of self-feeding received a high-calorie diet up to 120 days of age. The second group is experimental (MC-2): rats that were obtained from females with an experimental metabolic syndrome, but after switching to self-feeding received a standard diet. The third group is a control group of rats with a standard diet and water regime ad libitum. Mason-tricolor histochemical staining was used to determine collagen fibers, and immunohistochemical reaction using mouse Smooth Muscle Actin monoclonal antibodies (αSMA) was used to detect myofibroblasts. Results and discussion. It was found that the content of collagen fibers in the kidneys of the studied groups gradually increases with increasing of observation period, reaching maximum values on the 120th day of the study, with a statistically significant predominance of values in animals of group MC-1 over control animals in cortical and cerebral matter. Also, control and experimental groups are characterized by a gradual increase in the relative area occupied by αSMA+ cells from the total area of the organ, with maximum values at the end of the study. At the same time, there was a statistically significant predominance of the experimental groups MC-1 and MC-2 in the cortical substance in comparison with control animals. Conclusion. The gradual growth of collagen fibers in the cortical and cerebral substance is probably associated with an increase in the content of αSMA+ myofibroblasts, which according to research are markers of fibrosis

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