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Ampk ko mice

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https://www.readbyqxmd.com/read/29343420/ampk-re-activation-suppresses-hepatic-steatosis-but-its-downregulation-does-not-promote-fatty-liver-development
#1
Nadia Boudaba, Allison Marion, Camille Huet, Rémi Pierre, Benoit Viollet, Marc Foretz
Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism...
January 9, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29325933/sestrin2-prevents-age-related-intolerance-to-post-myocardial-infarction-via-ampk-pgc-1%C3%AE-pathway
#2
Nanhu Quan, Lin Wang, Xu Chen, Chelsea Luckett, Courtney Cates, Thomas Rousselle, Yang Zheng, Ji Li
We have revealed that a novel stress-inducible protein, Sestrin2, declines in the heart with aging. Moreover, there is an interaction between Sestrin2 and energy sensor AMPK in the heart in response to ischemic stress. The objective of this study is to determine whether Sestrin2-AMPK complex modulates PGC-1α in the heart and protects the heart from ischemic insults. In order to characterize the role of cardiac Sestrin2-AMPK signaling cascade in aging, C57BL/6 wild type young mice (3-4months), aged mice (24-26months) and young Sestrin2 KO mice were subjected to left anterior descending coronary artery occlusion for in vivo regional ischemia...
January 8, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29241457/impaired-regeneration-in-calpain-3-null-muscle-is-associated-with-perturbations-in-mtorc1-signaling-and-defective-mitochondrial-biogenesis
#3
Mehmet E Yalvac, Jakkrit Amornvit, Cilwyn Braganza, Lei Chen, Syed-Rehan A Hussain, Kimberly M Shontz, Chrystal L Montgomery, Kevin M Flanigan, Sarah Lewis, Zarife Sahenk
BACKGROUND: Previous studies in patients with limb-girdle muscular dystrophy type 2A (LGMD2A) have suggested that calpain-3 (CAPN3) mutations result in aberrant regeneration in muscle. METHODS: To gain insight into pathogenesis of aberrant muscle regeneration in LGMD2A, we used a paradigm of cardiotoxin (CTX)-induced cycles of muscle necrosis and regeneration in the CAPN3-KO mice to simulate the early features of the dystrophic process in LGMD2A. The temporal evolution of the regeneration process was followed by assessing the oxidative state, size, and the number of metabolic fiber types at 4 and 12 weeks after last CTX injection...
December 14, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29237572/the-role-of-adipor1-and-adipor2-in-liver-fibrosis
#4
Badr Alzahrani, Tristan Iseli, Mehdi Ramezani-Moghadam, Vikki Ho, Miriam Wankell, Eun Jin Sun, Liang Qiao, Jacob George, Lionel W Hebbard
Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model of liver fibrosis. In addition, we knocked down receptor function in primary hepatic stellate cells (HSCs) in vitro. Following the development of fibrosis, AdipoR1 and AdipoR2 KO mice had no quantitative difference in fibrosis by Sirius red staining...
December 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29170136/cereblon-deficiency-confers-resistance-against-polymicrobial-sepsis-by-the-activation-of-amp-activated-protein-kinase-and-heme-oxygenase-1
#5
Minchan Gil, Yun Kyu Kim, Ha Yeong Kim, Hyo-Kyung Pak, Chan-Sik Park, Kyung Jin Lee
Cereblon (CRBN) has a pleiotropic role in important cellular processes and is a potential therapeutic target in several diseases, including mental retardation, cancer, and metabolic disorders. The role of CRBN in polymicrobial sepsis induced by cecal ligation and puncture (CLP) was investigated using CRBN-deficient (KO) mice. Survival following CLP was significantly higher in KO mice compared to wild-type (WT) controls (50% vs 0% at day 6 after CLP). The improved survival of KO mice was accompanied by reduced peripheral blood bacterial load and lung injury...
November 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29167426/epigenetic-targeting-of-bromodomain-protein-brd4-counteracts-cancer-cachexia-and-prolongs-survival
#6
Marco Segatto, Raffaella Fittipaldi, Fabrizio Pin, Roberta Sartori, Kyung Dae Ko, Hossein Zare, Claudio Fenizia, Gianpietro Zanchettin, Elisa Sefora Pierobon, Shinji Hatakeyama, Cosimo Sperti, Stefano Merigliano, Marco Sandri, Panagis Filippakopoulos, Paola Costelli, Vittorio Sartorelli, Giuseppina Caretti
Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162538/metformin-promotes-the-proliferation-and-differentiation-of-murine-preosteoblast-by-regulating-the-expression-of-sirt6-and-oct4
#7
Wei Mu, Zhuoran Wang, Chuanyu Ma, Yunyun Jiang, Nannan Zhang, Kaiqiang Hu, Liyuan Li, Zhao Wang
Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin's effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast...
November 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29038293/loss-of-hepatic-amp-activated-protein-kinase-impedes-the-rate-of-glycogenolysis-but-not-gluconeogenic-fluxes-in-exercising-mice
#8
Curtis C Hughey, Freyja D James, Deanna P Bracy, E Patrick Donahue, Jamey D Young, Benoit Viollet, Marc Foretz, David H Wasserman
Pathologies including diabetes and conditions such as exercise place an unusual demand on liver energy metabolism, and this demand induces a state of energy discharge. Hepatic AMP-activated protein kinase (AMPK) has been proposed to inhibit anabolic processes such as gluconeogenesis in response to cellular energy stress. However, both AMPK activation and glucose release from the liver are increased during exercise. Here, we sought to test the role of hepatic AMPK in the regulation of in vivo glucose producing and citric acid cycle-related fluxes during an acute bout of muscular work...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29032027/peripheral-neuropathy-and-hindlimb-paralysis-in-a-mouse-model-of-adipocyte-specific-knockout-of-lkb1
#9
Yan Xiong, Jessica C Page, Naagarajan Narayanan, Chao Wang, Zhihao Jia, Feng Yue, Xine Shi, Wen Jin, Keping Hu, Meng Deng, Riyi Shi, Tizhong Shan, Gongshe Yang, Shihuan Kuang
Brown adipose tissues (BAT) burn lipids to generate heat through uncoupled respiration, thus representing a powerful target to counteract lipid accumulation and obesity. The tumor suppressor liver kinase b1 (Lkb1) is a key regulator of cellular energy metabolism; and adipocyte-specific knockout of Lkb1 (Ad-Lkb1 KO) leads to the expansion of BAT, improvements in systemic metabolism and resistance to obesity in young mice. Here we report the unexpected finding that the Ad-Lkb1 KO mice develop hindlimb paralysis at mid-age...
October 2017: EBioMedicine
https://www.readbyqxmd.com/read/28947430/sirt2-acts-as-a-cardioprotective-deacetylase-in-pathological-cardiac-hypertrophy
#10
Xiaoqiang Tang, Xiao-Feng Chen, Nan-Yu Wang, Xiao-Man Wang, Shu-Ting Liang, Wei Zheng, Yun-Biao Lu, Xiang Zhao, De-Long Hao, Zhu-Qin Zhang, Ming-Hui Zou, De-Pei Liu, Hou-Zao Chen
BACKGROUND: Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induced pathological cardiac hypertrophy. METHODS: Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy...
November 21, 2017: Circulation
https://www.readbyqxmd.com/read/28928671/aerobic-exercise-training-selectively-changes-oxysterol-levels-and-metabolism-reducing-cholesterol-accumulation-in-the-aorta-of-dyslipidemic-mice
#11
Guilherme Silva Ferreira, Paula R Pinto, Rodrigo T Iborra, Vanessa Del Bianco, Monique Fátima Mello Santana, Edna Regina Nakandakare, Valéria S Nunes, Carlos E Negrão, Sergio Catanozi, Marisa Passarelli
Background: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET) prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT) and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#12
Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Patrick Lahni, Basilia Zingarelli
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28874825/knockout-of-the-atpase-inhibitory-factor-1-protects-the-heart-from-pressure-overload-induced-cardiac-hypertrophy
#13
Kevin Yang, Qinqiang Long, Kamalamma Saja, Fengyuan Huang, Steven M Pogwizd, Lufang Zhou, Masasuke Yoshida, Qinglin Yang
Mitochondrial ATP synthase catalyzes the coupling of oxidative phosphorylation. Under pathological conditions, ATP synthase hydrolyzes ATP to replenish protons from the matrix into the intermembrane space, sustaining mitochondrial membrane potential. ATPase inhibitory factor 1 (IF1) is a nuclear-encoded, ATP synthase-interacting protein that selectively inhibits the hydrolysis activity of ATP synthase, which may render the protective role of IF1 in ischemic hearts. However, the in vivo cardiac function of IF1 and the potential therapeutic application targeting IF1 remain obscure...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28861078/increased-innate-lymphoid-cells-in-periodontal-tissue-of-the-murine-model-of-periodontitis-the-role-of-amp-activated-protein-kinase-and-relevance-for-the-human-condition
#14
Xu Qin, Md Nasrul Hoda, Cristiano Susin, Julie N Wheeler, Brendan Marshall, Libby Perry, Nancy Saad, Lin Yin, Ranya Elsayed, Mohammed Elsalanty, Rafik Abdelsayed, Jack C Yu, Krishnan M Dhandapani, Omid Akbari, Mahmood S Mozaffari, Babak Baban
Innate lymphoid cells (ILCs) are master regulators of immune and inflammatory responses, but their own regulatory mechanisms and functional roles of their subtypes (i.e., ILC1s-ILC3s) remain largely unresolved. Interestingly, AMP-activated protein kinase (AMPK), influences inflammatory responses, but its role in modulation of ILCs is not known. Periodontitis is a prevalent disorder with impairment of immune and inflammatory responses contributing importantly to its pathogenesis; however, neither the role of ILCs nor AMPK has been explored in this condition...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28844956/interleukin-6-deficiency-facilitates-myocardial-dysfunction-during-high-fat-diet-induced-obesity-by-promoting-lipotoxicity-and-inflammation
#15
Fan Chen, Dandan Chen, Xinmei Zhao, Shuai Yang, Zhe Li, Daniel Sanchis, Liang Jin, Xizhe Qiang, Kaiye Wang, Yitao Xu, Yubin Zhang, Junmei Ye
OBJECTIVE: Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. METHODS: Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28828587/tryptanthrin-prevents-oxidative-stress-mediated-apoptosis-through-amp-activated-protein-kinase-dependent-p38-mitogen-activated-protein-kinase-activation
#16
Eun Hye Jung, Ji Yun Jung, Hae Li Ko, Jae Kwang Kim, Sang Mi Park, Dae Hwa Jung, Chung A Park, Young Woo Kim, Sae Kwang Ku, Il Je Cho, Sang Chan Kim
Tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline) has been reported to have a variety of pharmacological activities. Present study investigated the cytoprotective effects of tryptanthrin on arachidonic acid (AA) + iron-mediated oxidative stress and the molecular mechanisms responsible. In HepG2 cells, pretreatment with tryptanthrin inhibited the cytotoxic effect of AA + iron in a concentration-dependent manner. In addition, tryptanthrin prevented the changes in the levels of apoptosis-related proteins, and attenuated reactive oxygen species production, glutathione depletion, and mitochondrial membrane impairment induced by AA + iron...
September 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28765264/anti-inflammatory-effects-of-exercise-training-in-adipose-tissue-do-not-require-fgf21
#17
Jay W Porter, Joe L Rowles, Justin A Fletcher, Terese M Zidon, Nathan C Winn, Leighton T McCabe, Young-Min Park, James W Perfield, John P Thyfault, R Scott Rector, Jaume Padilla, Victoria J Vieira-Potter
Exercise enhances insulin sensitivity; it also improves adipocyte metabolism and reduces adipose tissue inflammation through poorly defined mechanisms. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein whose insulin-sensitizing properties are predominantly mediated via receptor signaling in adipose tissue (AT). Recently, FGF21 has also been demonstrated to have anti-inflammatory properties. Meanwhile, an association between exercise and increased circulating FGF21 levels has been reported in some, but not all studies...
November 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28726277/aged-garlic-extract-suppresses-inflammation-in-apolipoprotein-e-knockout-mice
#18
Naoaki Morihara, Atsuko Hino, Satomi Miki, Miyuki Takashima, Jun-Ichiro Suzuki
SCOPE: Chronic inflammation plays a major role in the formation and progression of atherosclerotic plaques. To clarify the mode of action of aged garlic extract (AGE) to retard atherosclerosis, we investigated whether AGE suppresses the inflammation in apolipoprotein E-knockout (ApoE-KO) mice. METHODS AND RESULTS: ApoE-KO mice were fed standard diet with or without 3% AGE for 12 wk. AGE feeding inhibited the progression of atherosclerotic lesion by 27% and reduced the level of C-reactive protein (CRP) and thromboxane B2 (TXB2 ), a marker of platelet activation, in serum by 39 and 33%, respectively, compared to ApoE-KO mice without AGE treatment...
July 20, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28675237/ursolic-acid-induces-mitochondrial-biogenesis-through-the-activation-of-ampk-and-pgc-1-in-c2c12-myotubes-a-possible-mechanism-underlying-its-beneficial-effect-on-exercise-endurance
#19
Jihang Chen, Hoi Shan Wong, Pou Kuan Leong, Hoi Yan Leung, Wing Man Chan, Kam Ming Ko
Mitochondrial biogenesis, which involves an increase in mitochondrial number and the overall capacity of oxidative phosphorylation, is a critical determinant of skeletal muscle function. Recent findings have shown that some natural products can enhance mitochondrial adaptation to aerobic exercise, which in turn improves exercise performance, presumably by delaying muscle fatigue. Ursolic acid (UA), a natural triterpene, is commonly found in various vegetables and fruits. In the current study, UA was shown to increase mitochondrial mass and ATP generation capacity, with a concomitant production of a low level of mitochondrial reactive oxygen species (ROS) in C2C12 myotubes...
July 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28489607/trans-scirpusin-a-showed-antitumor-effects-via-autophagy-activation-and-apoptosis-induction-of-colorectal-cancer-cells
#20
Eun-Hye Hong, Eun-Young Heo, Jae-Hyoung Song, Bo-Eun Kwon, Jae-Young Lee, Yaejeong Park, Jinwoong Kim, Sun-Young Chang, Young-Won Chin, Sang-Min Jeon, Hyun-Jeong Ko
Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production...
June 20, 2017: Oncotarget
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