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AMPK AND Sirt1

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https://www.readbyqxmd.com/read/28192515/salmonella-typhimurium-disrupts-sirt1-ampk-checkpoint-control-of-mtor-to-impair-autophagy
#1
Raja Ganesan, Nina Judith Hos, Saray Gutierrez, Julia Fischer, Joanna Magdalena Stepek, Evmorphia Daglidu, Martin Krönke, Nirmal Robinson
During intracellular infections, autophagy significantly contributes to the elimination of pathogens, regulation of pro-inflammatory signaling, secretion of immune mediators and in coordinating the adaptive immune system. Intracellular pathogens such as S. Typhimurium have evolved mechanisms to circumvent autophagy. However, the regulatory mechanisms targeted by S. Typhimurium to modulate autophagy have not been fully resolved. Here we report that cytosolic energy loss during S. Typhimurium infection triggers transient activation of AMPK, an important checkpoint of mTOR activity and autophagy...
February 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28188344/skeletal-muscle-secretome-in-duchenne-muscular-dystrophy-a-pivotal-anti-inflammatory-role-of-adiponectin
#2
S Lecompte, M Abou-Samra, R Boursereau, L Noel, S M Brichard
BACKGROUND: Persistent inflammation exacerbates the progression of Duchenne muscular dystrophy (DMD). The hormone, adiponectin (ApN), which is decreased in the metabolic syndrome, exhibits anti-inflammatory properties on skeletal muscle and alleviates the dystrophic phenotype of mdx mice. Here, we investigate whether ApN retains its anti-inflammatory action in myotubes obtained from DMD patients. We unravel the underlying mechanisms by studying the secretome and the early events of ApN...
February 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28143892/activation-of-trpv4-by-dietary-apigenin-antagonizes-renal-fibrosis-in-deoxycorticosterone-acetate-doca-salt-induced-hypertension
#3
Xing Wei, Peng Gao, Yunfei Pu, Qiang Li, Tao Yang, Hexuan Zhang, Shiqiang Xiong, Yuanting Cui, Li Li, Xin Ma, Daoyan Liu, Zhiming Zhu
Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remain elusive. In this study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks...
January 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28112228/hormetic-effect-of-panaxatriol-saponins-confers-neuroprotection-in-pc12-cells-and-zebrafish-through-pi3k-akt-mtor-and-ampk-sirt1-foxo3-pathways
#4
Chao Zhang, Chuwen Li, Shenghui Chen, Zhiping Li, Lijuan Ma, Xuejing Jia, Kai Wang, Jiaolin Bao, Yeer Liang, Meiwan Chen, Peng Li, Huanxing Su, Simon Ming Yuen Lee, Kechun Liu, Jian-Bo Wan, Chengwei He
Hormesis is an adaptive response of living organisms to a moderate stress. However, its biomedical implication and molecular mechanisms remain to be intensively investigated. Panaxatriol saponins (PTS) is the major bioactive components extracted from Panax notoginseng, a widely used herbal medicine for cerebrovascular diseases. This study aims to examine the hormetic and neuroprotective effects of PTS in PC12 cells and zebrafish Parkinson's disease (PD) models. Our results demonstrated that PTS stimulated PC12 cell growth by about 30% at low doses, while PTS at high doses inhibited cell growth, which is a typical hormetic effect...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077576/specific-inhibition-of-acyl-coa-oxidase-1-by-an-acetylenic-acid-improves-hepatic-lipid-and-reactive-oxygen-species-ros-metabolism-in-rats-fed-a-high-fat-diet
#5
Jia Zeng, Senwen Deng, Yiping Wang, Ping Li, Lian Tang, Yefeng Pang
Chronic high-fat diet (HFD) results in hepatic mitochondrial dysfunction and induction of peroxisomal fatty acid oxidation (FAO), whether specific inhibition of peroxisomal FAO benefits mitochondrial FAO and reactive oxygen species (ROS) metabolism remains unclear. In this study, a specific inhibitor for the rate-limiting enzyme involved in peroxisomal FAO, acyl-CoA oxidase-1 (ACOX1) was developed and used for the investigation of peroxisomal FAO inhibition upon mitochondrial FAO and ROS metabolism. Specific inhibition of ACOX1 by 10,12 -tricosadiynoic acid increased hepatic mitochondrial FAO via activation of the SIRT1-AMPK pathway and PPARα and reduced hydrogen peroxide accumulation in high-fat diet fed rats, which significantly decreased hepatic lipid and ROS contents, reduced body weight gain and decreased serum triglyceride and insulin levels...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28063949/vitamin-d-supplementation-inhibits-oxidative-stress-and-upregulate-sirt1-ampk-glut4-cascade-in-high-glucose-treated-3t3l1-adipocytes-and-in-adipose-tissue-of-high-fat-diet-fed-diabetic-mice
#6
Prasenjit Manna, Arunkumar E Achari, Sushil K Jain
This study examined the hypothesis that vitamin-D prevents oxidative stress and upregulates glucose metabolism via activating insulin-independent signaling molecules in 3T3-L1 adipocytes and in high fat diet (HFD)-fed mice. To investigate the mechanism 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) (0-50 nM). Results showed that 1,25(OH)2D3 supplementation decreased NOX4 expression, ROS production, NF-κB phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells...
January 4, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28063518/role-of-nutraceutical-sirt1-modulators-in-ampk-and-mtor-pathway-evidence-of-a-synergistic-effect
#7
Luca Giovannini, Sara Bianchi
OBJECTIVE: The aim of this study was to evaluate the effect of different natural substances on SIRT1 expression and on AMPK and mTOR phosphorylation. Moreover, we investigated the presence of a synergistic effect between the substances. METHODS: Human cervical carcinoma cells were seeded in 12-well plates, then incubated with the nine tested substances (resveratrol, quercetin, berberine, catechin, tyrosol, ferulic acid, niclosamide, curcumin, and malvidin) at different concentrations and left in incubation for 3, 6, and 24 h...
February 2017: Nutrition
https://www.readbyqxmd.com/read/28006433/intracerebroventricular-tempol-administration-in-older-rats-reduces-oxidative-stress-in-the-hypothalamus-but-does-not-change-stat3-signalling-or-sirt1-ampk-pathway
#8
Hale Z Toklu, Philip J Scarpace, Yasemin Sakarya, Nataliya Kirichenko, Michael Matheny, Erin B Bruce, Christy S Carter, Drake Morgan, Nihal Tümer
Hypothalamic inflammation and increased oxidative stress are believed to be mechanisms that contribute to obesity. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol), a free radical scavenger, has been shown to reduce inflammation and oxidative stress. We hypothesized that brain infusion of tempol would reduce oxidative stress, and thus would reduce food intake and body weight and improve body composition in rats with age-related obesity and known elevated oxidative stress. Furthermore, we predicted an associated increase in markers of leptin signalling, including the silent mating type information regulator 2 homolog 1 (SIRT1)/5'AMP-activated protein kinase (AMPK) pathway and the signal transducer and activator of transcription 3 (STAT3) pathway...
January 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/27998210/metabolic-stress-induces-cognitive-disturbances-and-inflammation-in-aged-mice-protective-role-of-resveratrol
#9
Veronica Palomera-Ávalos, Christian Griñán-Ferré, Vanesa Izquierdo, Antonio Camins, Coral Sanfeliu, Mercè Pallàs
Inflammation and oxidative stress (OS) are key points in age progression. Both processes impact negatively in cognition and in brain functions. Resveratrol (RV) has been postulated as a potent antioxidant natural compound, with rejuvenating properties. Inducing a metabolic stress by high-fat (HF) diet in aged C56/BL6 (24 months) led to cognitive disturbances compared with control age mated and with young mice. These changes were prevented by RV. Molecular determinations demonstrated a significant increase in some inflammatory parameters (TNF-α, Cxcl10, IL-1, IL-6, and Ccl3) in old mice, but slight changes in OS machinery...
January 25, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/27986499/targeting-chromatin-aging-the-epigenetic-impact-of-longevity-associated-interventions
#10
Adam E Field, Peter D Adams
A rapidly growing body of evidence has shown that chromatin undergoes radical alterations as an organism ages, but how these changes relate to aging itself is an open question. It is likely that these processes contribute to genomic instability and loss of transcriptional fidelity, which in turn drives deleterious age-related phenotypes. Interventions associated with increased healthspan and longevity such as reduced insulin/IGF signalling (IIS), inhibition of mTOR and energy depletion resulting in SIRT1/AMPK activation, all have beneficial effects which ameliorate multiple facets of age-associated decline...
December 13, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27980001/exogenous-thyroxine-improves-glucose-intolerance-in-insulin-resistant-rats
#11
Guillermo Vazquez-Anaya, Bridget Martinez, José G Soñanez-Organis, Daisuke Nakano, Akira Nishiyama, Rudy M Ortiz
Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T4) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T4 (8...
March 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27966786/fibroblast-growth-factor-21-fgf21-promotes-formation-of-aerobic-myofibers-via-the-fgf21-sirt1-ampk-pgc1%C3%AE-pathway
#12
Xinyi Liu, Yongliang Wang, Liming Hou, Yuanzhu Xiong, Shuhong Zhao
Fibroblast growth factor 21(FGF21) is a pivotal regulator of energy metabolism, which is currently being assessed as a potential drug target for the treatment of insulin-resistant conditions. However, the cellular mechanisms by which FGF21 affects myogenesis remain unclear. In this study, we explored the function of FGF21 in myogenesis both in vitro and in vivo. Our experiments showed for the first time that FGF21 promotes myoblast differentiation and serves as a switch of molecular transformation from anaerobic myofibers to aerobic myofibers via the FGF21-SIRT1-AMPK-PGC1α axis...
December 14, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27956176/glucagon-like-peptide-1-effects-lipotoxic-oxidative-stress-by-regulating-the-expression-of-micrornas
#13
Zhiying Zhang, Huifang Liu, Qiang Li
Aim to confirm whether the treatment of GLP-1 can modulated body weight, lipid metabolism, insulin content, pancreas oxidative stress, improved T-AOC, MDA levels related to FFA-Induced oxidative stress in C57BL/6 mice and INS-1 cells. In this study, GLP-1 makes the expression of AMPK, PPARα, CPT1A and SIRT1 increased, and the expression of SREBP1c, miR-33 and miR-370 decreased. Interestingly, the effects of GLP-1 were less dose dependent as GLP-1 regulated the FFA, which related to gene expression at much lower doses (3 μg/kg, 10 mM, mice and INS-1 respectively) and effects were relatively maintained at higher dose (30 μg/kg, 100 mM, mice and INS-1 respectively) as well...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27917437/nicotine-plus-a-high-fat-diet-triggers-cardiomyocyte-apoptosis
#14
Indrani Sinha-Hikim, Theodore C Friedman, Mark Falz, Victor Chalfant, Mohammad Kamrul Hasan, Jorge Espinoza-Derout, Desean L Lee, Carl Sims, Peter Tran, Sushil K Mahata, Amiya P Sinha-Hikim
Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis. Given that CM apoptosis has been implicated as a potential mechanism in the development of cardiomyopathy and heart failure, we characterize the key signaling pathways in nicotine plus high-fat diet (HFD)-induced CM apoptosis. Adult C57BL6 male mice were fed a normal diet (ND) or HFD and received twice-daily intraperitoneal (IP) injections of nicotine (0...
December 5, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27897112/harnessing-the-power-of-sirt1-and-non-coding-rnas-in-vascular-disease
#15
Kenneth Maiese
Noncommunicable diseases (NCDs) contribute to a significant amount of disability and death in the world. Of these disorders, vascular disease is ranked high, falls within the five leading causes of death, and impacts multiple other disease entities such as those of the cardiac system, nervous system, and metabolic disease. Targeting the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) pathway and the modulation of micro ribonucleic acids (miRNAs) may hold great promise for the development of novel strategies for the treatment of vascular disease since each of these pathways are highly relevant to cardiac and nervous system disorders as well as to metabolic dysfunction...
November 29, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27871084/olmesartan-prevents-microalbuminuria-in-db-db-diabetic-mice-through-inhibition-of-angiotensin-ii-p38-sirt1-induced-podocyte-apoptosis
#16
Junhui Gu, Ming Yang, Na Qi, Shuqin Mei, Jiejian Chen, Shuwei Song, Ying Jing, Meihan Chen, Liangliang He, Lijun Sun, Huimin Hu, Lin Li, Rudolf P Wüthrich, Ming Wu, Changlin Mei
BACKGROUND/AIMS: Blockage of the renin-angiotensin II system (RAS) prevents or delays albuminuria in diabetic patients. The aim of this study was to investigate the inhibitory mechanism of the angiotensin receptor blocker olmesartan on albuminuria in a murine model of diabetic nephropathy. METHODS: Male db/db diabetic mice were fed with placebo or 20 mg/kg olmesartan by daily gavage for 12 weeks. Conditionally immortalized mouse podocytes were treated with glucose, angiotensin II, olmesartan or p38 inhibitor s8307 in different experimental conditions after differentiation...
2016: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/27836811/sirt1-ampk-crosstalk-is-involved-in-high-glucose-dependent-impairment-of-insulin-responsiveness-in-primary-rat-podocytes
#17
Dorota Rogacka, Agnieszka Piwkowska, Irena Audzeyenka, Stefan Angielski, Maciej Jankowski
Growing evidence indicates that in diabetes, high glucose concentrations affect podocyte metabolism and function. The crucial pathological feature of type 2 diabetes mellitus and metabolic syndrome is insulin resistance, often developed as a result of dysregulation of nutrient-responsible systems and disturbance of cellular homeostasis under diabetic conditions. Here, we report the involvement of the reciprocal interplay between deacetylase SIRT1 and protein kinase AMPK in podocyte high glucose-induced abolition of insulin-dependent glucose uptake, manifesting insulin resistance...
November 9, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27830023/over-expression-of-heat-shock-protein-70-protects-mice-against-lung-ischemia-reperfusion-injury-through-sirt1-ampk-enos-pathway
#18
Shumei Liu, Junping Xu, Chunfang Fang, Chunjing Shi, Xin Zhang, Bo Yu, Yantong Yin
Lung ischemia/reperfusion injury (LIRI) usually occurs during in lung transplantation and extracorporeal circulation operation and may develop into pulmonary infections, acute rejection and bronchiolitis obliterans syndrome. Recent studies have discovered the protective effect of heat shock protein 70 (HSP70) on various types of injuries. In the present study, we firstly explore the role of over-expressed HSP70 on the protection against LIRI. Lung Wet/Dry (W/D) ratio, biomarkers in the bronchoalveolar lavage fluid (BALF), lung histological changes and apoptosis markers, oxidative products and proinflammatory cytokines in the lung tissues were analyzed...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27824080/lycium-barbarum-polysaccharide-attenuates-high-fat-diet-induced-hepatic-steatosis-by-up-regulating-sirt1-expression-and-deacetylase-activity
#19
Li Jia, Wang Li, Jianning Li, Yan Li, Hui Song, Yansong Luan, Hui Qi, Lirong Ma, Xiaohong Lu, Yi Yang
In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD(+)/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27760313/a-mathematical-model-of-the-liver-circadian-clock-linking-feeding-and-fasting-cycles-to-clock-function
#20
Aurore Woller, Hélène Duez, Bart Staels, Marc Lefranc
To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock, incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various temporal patterns of AMPK activation was simulated numerically, mimicking the effects of a normal diet, fasting, and a high-fat diet...
October 18, 2016: Cell Reports
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