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Ampk ko mice

Tetsuya Kubota, Naoto Kubota, Hiroyuki Sato, Mariko Inoue, Hiroki Kumagai, Tomokatsu Iwamura, Iseki Takamoto, Tsuneo Kobayashi, Masao Moroi, Yasuo Terauchi, Kazuyuki Tobe, Kohjiro Ueki, Takashi Kadowaki
The aim of this study is to elucidate to what degree adiponectin is involved in TZD-mediated amelioration of neointimal formation. We investigated the effect of 3- or 8-weeks' pioglitazone on cuff-induced neointimal formation in adiponectin-deficient (APN-KO) and wild-type (WT) mice. Pioglitazone for 3 weeks reduced neointimal formation in the WT mice with upregulation of the plasma adiponectin levels, but failed to reduce neointimal formation in the APN-KO mice, suggesting that pioglitazone suppressed neointimal formation by adiponectin-dependent mechanisms...
October 5, 2016: Scientific Reports
Tarek A M Almabrouk, Azizah B Ugusman, Omar J Katwan, Ian P Salt, Simon Kennedy
BACKGROUND: Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin which produce a net anticontractile effect in healthy PVAT. AMP-activated protein kinase (AMPK) is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. METHODS: Endothelium-denuded aortic rings from wild-type (Sv129) and α1 AMPK knockout (KO) mice were mounted on a wire myograph...
September 26, 2016: British Journal of Pharmacology
Ki Churl Chang, Young Shin Ko, Hye Jung Kim, Da-Yeong Nam, Dong-Ung Lee
High mobility group box 1 (HMGB1), a late phase cytokine of sepsis, is viewed as a potential target for the treatment of sepsis. The authors considered that 13-methylberberine (13-MB) might reduce circulating HMGB1 levels and increase survival in a mouse model of sepsis by activating AMP-activated protein kinase (AMPK). Western blot analysis and vascular contraction testing were performed using RAW264.7 cells and rat thoracic aorta, respectively. The mechanisms responsible were investigated using various signal inhibitors and small interfering RNA techniques...
September 12, 2016: International Immunopharmacology
Yusuke Nakatsu, Yasuka Matsunaga, Takeshi Yamamotoya, Koji Ueda, Yuki Inoue, Keiichi Mori, Hideyuki Sakoda, Midori Fujishiro, Hiraku Ono, Akifumi Kushiyama, Tomoichiro Asano
Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer's disease...
2016: International Journal of Molecular Sciences
Ping Ke, Bo-Zong Shao, Zhe-Qi Xu, Wei Wei, Bin-Ze Han, Xiong-Wen Chen, Ding-Feng Su, Chong Liu
Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1)...
2016: PloS One
Susana Rodriguez, Xia Lei, Pia S Petersen, Stefanie Y Tan, Hannah C Little, G William Wong
C1q/TNF-related protein 1 (CTRP1) is a conserved plasma protein of the C1q family with notable metabolic and cardiovascular functions. We have previously shown that CTRP1 infusion lowers blood glucose and that transgenic mice with elevated circulating CTRP1 are protected from diet-induced obesity and insulin resistance. Here, we used a genetic loss-of-function mouse model to address the requirement of CTRP1 for metabolic homeostasis. Despite similar body weight, food intake, and energy expenditure, Ctrp1 knockout (KO) mice fed a low-fat diet developed insulin resistance and hepatic steatosis...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Orhan Efe, Janet D Klein, Lauren M LaRocque, Huiwen Ren, Jeff M Sands
Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/ kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily...
July 21, 2016: JCI Insight
Jacqueline A Bayliss, Moyra B Lemus, Vanessa V Santos, Minh Deo, Jeffrey S Davies, Bruce E Kemp, John D Elsworth, Zane B Andrews
Metformin is a widely prescribed drug used to treat type-2 diabetes, although recent studies show it has wide ranging effects to treat other diseases. Animal and retrospective human studies indicate that Metformin treatment is neuroprotective in Parkinson's Disease (PD), although the neuroprotective mechanism is unknown, numerous studies suggest the beneficial effects on glucose homeostasis may be through AMPK activation. In this study we tested whether or not AMPK activation in dopamine neurons was required for the neuroprotective effects of Metformin in PD...
2016: PloS One
Tizhong Shan, Yan Xiong, Pengpeng Zhang, Zhiguo Li, Qingyang Jiang, Pengpeng Bi, Feng Yue, Gongshe Yang, Yizhen Wang, Xiaoqi Liu, Shihuan Kuang
Brown adipose tissue (BAT) dissipates energy through Ucp1-mediated uncoupled respiration and its activation may represent a therapeutic strategy to combat obesity. Here we show that Lkb1 controls BAT expansion and UCP1 expression in mice. We generate adipocyte-specific Lkb1 knockout mice and show that, compared with wild-type littermates, these mice exhibit elevated UCP1 expression in BAT and subcutaneous white adipose tissue, have increased BAT mass and higher energy expenditure. Consequently, KO mice have improved glucose tolerance and insulin sensitivity, and are more resistant to high-fat diet (HFD)-induced obesity...
2016: Nature Communications
Jonathan F Gill, Julien Delezie, Gesa Santos, Christoph Handschin
OBJECTIVE: Food intake and whole-body energy homeostasis are controlled by agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons located in the arcuate nucleus of the hypothalamus. Key energy sensors, such as the AMP-activated protein kinase (AMPK) or sirtuin 1 (SIRT1), are essential in AgRP and POMC cells to ensure proper energy balance. In peripheral tissues, the transcriptional coactivator PGC-1α closely associates with these sensors to regulate cellular metabolism...
July 2016: Molecular Metabolism
Ying Chen, Surendra Singh, Akiko Matsumoto, Soumen K Manna, Mohamed A Abdelmegeed, Srujana Golla, Robert C Murphy, Hongbin Dong, Byoung-Joon Song, Frank J Gonzalez, David C Thompson, Vasilis Vasiliou
The pathogenesis of alcoholic liver disease (ALD) is not well established. However, oxidative stress and associated decreases in levels of glutathione (GSH) are known to play a central role in ALD. The present study examines the effect of GSH deficiency on alcohol-induced liver steatosis in Gclm knockout (KO) mice that constitutively have ≈15% normal hepatic levels of GSH. Following chronic (6 week) feeding with an ethanol-containing liquid diet, the Gclm KO mice were unexpectedly found to be protected against steatosis despite showing increased oxidative stress (as reflected in elevated levels of CYP2E1 and protein carbonyls)...
2016: Scientific Reports
Jingjing Wang, Yao Song, Hao Li, Qiang Shen, Jing Shen, Xiangbo An, Jimin Wu, Jianshu Zhang, Yunong Wu, Han Xiao, Youyi Zhang
Senescent hearts exhibit defective responses to β-adrenergic receptor (β-AR) over-activation upon stress, leading to more severe pathological cardiac remodelling. However, the underlying mechanisms remain unclear. Here, we investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in protecting against ageing-associated cardiac remodelling in mice upon β-AR over-activation. 10-week-old (young) and 18-month-old (old) mice were subcutaneously injected with the β-AR agonist isoproterenol (ISO) (5 mg/kg)...
July 8, 2016: Clinical and Experimental Pharmacology & Physiology
Gantsetseg Tumurkhuu, Kenichi Shimada, Jargalsaikhan Dagvadorj, Timothy R Crother, Wenxuan Zhang, Daniel Luthringer, Roberta A Gottlieb, Shuang Chen, Moshe Arditi
RATIONALE: Activation of NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediating interleukin (IL)-1β secretion has emerged as an important component of inflammatory processes in atherosclerosis. Mitochondrial DNA (mtDNA) damage is detrimental in atherosclerosis, and mitochondria are central regulators of the nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 inflammasome. Human atherosclerotic plaques express increased mtDNA damage...
September 2, 2016: Circulation Research
Mayte Alvarez-Crespo, Robert I Csikasz, Noelia Martínez-Sánchez, Carlos Diéguez, Barbara Cannon, Jan Nedergaard, Miguel López
OBJECTIVE: Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice...
April 2016: Molecular Metabolism
J Craps, V Joris, B De Jongh, P Sonveaux, S Horman, B Lengelé, L Bertrand, M-C Many, I M Colin, A-C Gérard
Iodine deficiency (ID) induces TSH-independent microvascular activation in the thyroid via the reactive oxygen species/nitric oxide-hypoxia-inducible factor-1α/vascular endothelial growth factor (VEGF) pathway. We hypothesized the additional involvement of mammalian target of rapamycin (mTOR) as a positive regulator of this pathway and AMP-activated protein kinase (AMPK) as a negative feedback regulator to explain the transient nature of ID-induced microvascular changes under nonmalignant conditions. mTOR and AMPK involvement was investigated using an in vitro model (human thyrocytes in primary cultures) and 2 murine models of goitrogenesis (normal NMRI and RET-PTC mice [a papillary thyroid cancer model])...
June 2016: Endocrinology
Justin A Fletcher, Melissa A Linden, Ryan D Sheldon, Grace M Meers, E Matthew Morris, Anthony Butterfield, James W Perfield, John P Thyfault, R Scott Rector
Exercise stimulates hepatic mitochondrial adaptations; however, the mechanisms remain largely unknown. Here we tested whether FGF21 plays an obligatory role in exercise induced hepatic mitochondrial adaptations by testing exercise responses in FGF21 knockout mice. FGF21 knockout (FGF21-KO) and wild-type (WT) mice (11-12 wk of age) had access to voluntary running wheels for exercise (EX) or remained sedentary for 8 wk. FGF21 deficiency resulted in greater body weight, adiposity, serum cholesterol, insulin, and glucose concentrations compared with WT mice (P < 0...
May 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sophie R Sayers, Frank Reimann, Fiona M Gribble, Helen Parker, Sagen Zac-Varghese, Stephen R Bloom, Marc Foretz, Benoit Viollet, Guy A Rutter
BACKGROUND: Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1) in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK) in these cells. METHOD: Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre) to catalyse recombination of floxed alleles of AMPKα1 and α2...
2016: PloS One
Ailian Tang, Can Li, Nan Zou, Qian Zhang, Meiling Liu, Xia Zhang
AIMS: Recent evidences suggest that angiotensin-(1-7) [Ang-(1-7)] could improve non-alcoholic steatohepatitis (NASH) via adiponectin-dependent mechanism. This study was aimed to investigate whether and how Ang-(1-7) influences NASH without adiponectin. METHODS: Adiponectin knockout (KO) mice were fed with high fat diet (HFD) or normal chow for six months, subsequently infused with Ang-(1-7) or saline for two weeks. RESULTS: We found that HFD fed mice exhibited obesity, hyperlipidemia, NASH, and significantly increased levels of serum Ang-(1-7)...
March 18, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Jacqueline A Bayliss, Moyra B Lemus, Romana Stark, Vanessa V Santos, Aiysha Thompson, Daniel J Rees, Sandra Galic, John D Elsworth, Bruce E Kemp, Jeffrey S Davies, Zane B Andrews
Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect...
March 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tae-Won Kim, Young-Jung Kim, Hyun-Tae Kim, Se-Ra Park, Mee-Young Lee, Yong-Deok Park, Chul-Ho Lee, Ju-Young Jung
AIMS: Recent studies have revealed that autophagy is induced under various disease conditions; however, the role of autophagy in pathological states is controversial. NAD(P)H: quinone oxidoreductase 1 (NQO1) is a highly inducible cytoprotective gene that regulates reactive oxygen species (ROS) generation. In this study, we examined whether NQO1 deficiency affects the autophagy process in response to cisplatin-induced nephrotoxicity. RESULTS: In vitro, NQO1 and autophagy-associated proteins were induced after cisplatin treatment and the autophagosomes markedly increased in the cisplatin-treated NQO1-knockdown ACHN cells together with increased ROS production...
May 20, 2016: Antioxidants & Redox Signaling
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