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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28480026/exercise-training-provides-cardioprotection-by-activating-and-coupling-endothelial-nitric-oxide-synthase-via-a-%C3%AE-3-adrenergic-receptor-amp-activated-protein-kinase-signaling-pathway
#14
Larry A Barr, Jonathan P Lambert, Yuuki Shimizu, Lili A Barouch, Nawazish Naqvi, John W Calvert
Exercise training confers sustainable protection against ischemia/reperfusion injury. However, the mechanism by which this process occurs is not fully understood. Previously, it was shown that β3-adrenergic receptors (β3-ARs) play a critical role in regulating the activation of endothelial nitric oxide synthase (eNOS) in response to exercise and play a critical role in exercise-mediated cardioprotection. Intriguingly, a deficiency in β3-ARs led to increased myocardial injury following exercise training. The purpose of the current study was to determine mechanisms by which β3-ARs are linked to eNOS activation and to determine the mechanism responsible for the exacerbated ischemia/reperfusion injury displayed by β3-AR deficient (β3-AR KO) mice after exercise training...
January 2017: Medical Gas Research
https://www.readbyqxmd.com/read/28477305/long-term-obestatin-treatment-of-mice-type-2-diabetes-increases-insulin-sensitivity-and-improves-liver-function
#15
Paweł A Kołodziejski, Ewa Pruszyńska-Oszmałek, Mathias Z Strowski, Krzysztof W Nowak
PURPOSE: Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). METHODS: The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized...
June 2017: Endocrine
https://www.readbyqxmd.com/read/28474247/inhibition-of-angiotensin-ii-induced-cardiac-fibrosis-by-atorvastatin-in-adiponectin-knockout-mice
#16
Sun Young Choi, Jong Sung Park, Mee Sook Roh, Chong-Rak Kim, Moo Hyun Kim, Victor Serebruany
Adiponectin is a polypeptide known to inhibit cardiac fibrosis via the activation of ‎adenosine monophosphate-activated protein kinase (AMPK). Statins can also activate AMPK, resulting in the secretion of adiponectin. We determined whether atorvastatin inhibits angiotensin II-induced cardiac fibrosis (AICF) in the presence or absence of adiponectin. Adiponectin knockout (APN-KO, n = 44) and wild type (WT, n = 44) mice were received subcutaneous angiotensin II (1.5 mg/kg/day), and atorvastatin (10 mg/kg/day) was administered orally for 15 days...
May 2017: Lipids
https://www.readbyqxmd.com/read/28472467/hypothalamic-regulation-of-liver-and-muscle-nutrient-partitioning-by-brain-specific-carnitine-palmitoyltransferase-1c-in-male-mice
#17
Macarena Pozo, Rosalía Rodríguez-Rodríguez, Sara Ramírez, Patricia Seoane-Collazo, Miguel López, Dolors Serra, Laura Herrero, Núria Casals
Carnitine palmitoyltransferase (CPT) 1C, a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions. Based on global knockout (KO) models, CPT1C has demonstrated relevance in hippocampus-dependent spatial learning and in hypothalamic regulation of energy balance. Specifically, it has been shown that CPT1C is protective against high-fat diet-induced obesity (DIO), and that CPT1C KO mice show reduced peripheral fatty acid oxidation (FAO) during both fasting and DIO...
July 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28389470/rac1-and-ampk-account-for-the-majority-of-muscle-glucose-uptake-stimulated-by-ex-vivo-contraction-but-not-in-vivo-exercise
#18
Lykke Sylow, Lisbeth L V Møller, Maximilian Kleinert, Gommaar D'Hulst, Estelle De Groote, Peter Schjerling, Gregory R Steinberg, Thomas E Jensen, Erik A Richter
Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin-resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake, but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss of function combined with either pharmacological inhibition or genetic deletion of Rac1...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28179232/kidney-specific-genetic-deletion-of-both-ampk-%C3%AE-subunits-causes-salt-and-water-wasting
#19
Yoskaly Lazo-Fernández, Goretti Baile, Patricia Meade, Pilar Torcal, Laura Martínez, Carmen Ibañez, Maria Luisa Bernal, Benoit Viollet, Ignacio Giménez
AMP-activated kinase (AMPK) controls cell energy homeostasis by modulating ATP synthesis and expenditure. In vitro studies have suggested AMPK may also control key elements of renal epithelial electrolyte transport but in vivo physiological confirmation is still insufficient. We studied sodium renal handling and extracellular volume regulation in mice with genetic deletion of AMPK catalytic subunits. AMPKα1 knockout (KO) mice exhibit normal renal sodium handling and a moderate antidiuretic state. This is accompanied by higher urinary aldosterone excretion rates and reduced blood pressure...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28135761/palmitoleic-acid-reduces-the-inflammation-in-lps-stimulated-macrophages-by-inhibition-of-nf%C3%AE%C2%BAb-independently-of-ppars
#20
Camila O Souza, Alexandre A S Teixeira, Luana A Biondo, Loreana S Silveira, Philip Calder, José C Rosa Neto
Palmitoleic acid (PM, 16:1n-7) has anti-inflammatory properties that could be linked to higher expression of PPARα, an inhibitor of NFκB. Macrophages play a major role in the pathogenesis of chronic inflammation, however, the effects of PM on macrophages are underexplored. Thus, we aimed to investigate the effects of PM in activated macrophages as well the role of PPARα. Primary macrophages were isolated from C57BL6 (WT) and PPARα knockout (KO) mice, cultured under standard conditions and exposed to LPS (2...
January 30, 2017: Clinical and Experimental Pharmacology & Physiology
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