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Yunu Jung, Jinbong Park, Hye-Lin Kim, Jung-Eun Sim, Dong-Hyun Youn, JongWook Kang, Seona Lim, Mi-Young Jeong, Woong Mo Yang, Seok-Geun Lee, Kwang Seok Ahn, Jae-Young Um
Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice...
November 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
San-Yuan Chen, Chun-Hsiang Lin, Jiun-Tsai Lin, Yi-Fang Cheng, Han-Min Chen, Shao-Hsuan Kao
AMP-activated protein kinase (AMPK) is known as a pivotal regulator of cellular metabolism. Mounting evidences have demonstrated that AMPK activation exerts tumor suppressive activity on leukemia cells. The present study reported that adenine, an AMPK activator, triggers cell cycle arrest and autophagy of human chronic myelogenous leukemia K562 cells consequently suppressing cell viability. The present findings revealed that adenine treatment (4.0-8.0 mM) significantly inhibited the viability of K562 cells to 69...
November 2017: Oncology Letters
Jun Huang, Ke Liu, Shan Zhu, Min Xie, Rui Kang, Lizhi Cao, Daolin Tang
Sepsis and septic shock remain challenging for intensive care units worldwide and have limited treatment options; therefore, identification of targetable key players in systemic inflammation and multiple organ failure is urgently needed. Here, we show that AMP-activated protein kinase (AMPK) is a negative regulator of bioenergetic reprogramming in immune cells and suppresses sepsis development in vivo. Mechanistically, AMPK deficiency increases pyruvate kinase isozyme M2 (PKM2)-dependent aerobic glycolysis, which leads to the release of high mobility group box 1 (HMGB1, a late mediator of lethal systemic inflammation) in macrophages and monocytes...
November 3, 2017: Brain, Behavior, and Immunity
Wojciech Bobela, Sameer Nazeeruddin, Graham Knott, Patrick Aebischer, Bernard L Schneider
BACKGROUND: Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson's disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefore contribute to neurodegeneration. METHODS: Here, we overexpress various genetic variants of the catalytic AMPKα subunit to determine how AMPK activity affects the survival and function of neurons overexpressing human α-synuclein in vivo. RESULTS: Both AMPKα1 and α2 subunits have neuroprotective effects against human α-synuclein toxicity in nigral dopaminergic neurons...
November 3, 2017: Molecular Neurodegeneration
Lingli Zheng, Lianhong Yin, Lina Xu, Yan Qi, Hua Li, Youwei Xu, Xu Han, Kexin Liu, Jinyong Peng
Our previous works showed that dioscin, a natural product, could protect liver from acute liver damages induced by dimethylnitrosamine, ethanol, carbon tetrachloride and acetaminophen. However, the effect of dioscin on thioacetamide (TAA)-induced acute liver injury still remained unknown. The purpose of this study was to investigate whether dioscin confers a protective effect against TAA-induced acute liver injury in rats and mice. The results showed that dioscin decreased the serum levels of ALT, AST, and rehabilitated histopathological changes compared with the model groups...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wen Wu, Kai-Lun Liang, Bo Chen, Jie Su, Su-Hong Chen, Gui-Yuan Lyu
To study the anti-obesity effect of Mori Folium extract on diet-induced obesity(DIO) and to explore the preliminary mechanism in rats. DIO rat models were established by high glucose and high fat diet for 8 weeks. Then high(10 mg•kg⁻¹) and low(5 mg•kg⁻¹) does Mori Folium extracts were given by intragastric administration for 13 weeks. After the last administration, their body weight, 24 h food intake, water intake, Lee's index, liver/body mass index, and fat/body mass index were determined. The levels of lipoprotein lipase(LPL), CCAAT/enhancer-binding protein alpha(C/EBPα) and peroxisome proliferator-activated receptor gamma(PPARγ) were measured by enzyme-linked immunosorbent assay(ELISA)...
May 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Se Hyun Kim, Soyoung Park, Hyun Sook Yu, Kyung Hee Ko, Hong Geun Park, Yong Sik Kim
Clozapine, a representative atypical antipsychotic, has superior efficacy compared to other antipsychotic agents and is used for the treatment of severe psychotic disorders. Therefore, studies on its mechanisms of action are important for understanding the mechanisms of therapeutic approaches to psychosis. Adenosine monophosphate-activated protein kinase (AMPK) is a serine-threonine kinase that plays a major role in maintaining metabolic homeostasis. Unc-51-like kinase 1 (ULK1) and Beclin1 are downstream substrates of AMPK and activate the autophagic process...
October 25, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Dong-Xin Sui, Hui-Min Zhou, Feng Wang, Ming Zhong, Wei Zhang, Yun Ti
AIMS: CIDEC was proven to be closely associated with the development of insulin resistance and metabolic syndrome. We aimed to investigate whether the CIDEC gene silencing could alleviate pulmonary vascular remodeling in a type 2 diabetic rat model. MATERIALS AND METHODS: We built a type 2 diabetic rat model. An adenovirus harboring CIDEC small interfering RNA (siRNA) was then injected via the jugular vein to silence the CIDEC gene. After HE and Sirius red staining, we detected indexes of the pulmonary arterioles remodeling...
October 27, 2017: Journal of Diabetes Investigation
Jinbao Huang, Yibin Zhou, Bei Wan, Qiushi Wang, Xiaochun Wan
Our previous results showed that green tea polyphenols (GTPs) significantly altered the expression of lipid-metabolizing genes in the liver of chickens. However, the underlying mechanism was not elucidated. In this study, we further characterized how GTPs influence AMP-activated protein kinase (AMPK) in the regulation of hepatic fat metabolism. Thirty-six male chickens were fed GTPs at a daily dose of 0, 80 or 160 mg/kg of body weight for 4 weeks. The results demonstrated that oral administration of GTPs significantly reduced hepatic lipid content and abdominal fat mass, enhanced the phosphorylation levels of AMPKα and ACACA, and altered the mRNA levels and enzymatic activities of lipid-metabolizing enzymes in the liver...
2017: PloS One
Joon-Seung Han, Jong Hwan Sung, Seung Kwon Lee
GINST, a hydrolyzed ginseng extract, has been reported to have antidiabetic effects and to reduce hyperglycemia and hyperlipidemia. Hypercholesterolemia is caused by diet or genetic factors and can lead to atherosclerosis and coronary heart disease. Thus, the purpose of this study is to determine whether GINST and the ginsenoside metabolite, IH-901 (compound K), reduce cholesterol synthesis in HepG2 cells and the signal transduction pathways involved. Concentrations of cholesterol were measured by using an enzymatic method...
October 24, 2017: Journal of Food Science
Xin Tao, Lei Chen, Lisi Cai, Shuqi Ge, Xuanying Deng
In order to preliminarily explore the correlation between the AMPKα-SIRT1 pathway and insulin resistance and reproductive function in PCOS mice and find the pathogenesis molecular mechanism and potential therapeutic target of PCOS, we carried out in vitro study of human granulosa KGN cells and in vivo study of PCOS mouse model which was constructed with DHEA, and AICAR and Compound C were applied. We have found that SIRT1 and AMPKα expression in KGN cells gradually decreased as DHEA concentration increased; Mice of the PCOS model were in an obvious status of IR (P < 0...
October 5, 2017: Biochemical and Biophysical Research Communications
Yang Gu, Lu Gao, Yu Chen, Zhuo Xu, Kun Yu, Dongying Zhang, Gang Zhang, Xiwen Zhang
Sanggenon C is isolated from Morus alba, a plant that has been used for anti‑inflammatory purposes in Oriental medicine. Little is known about the effect of Sanggenon C on cardiomyocyte hypoxia injury. This study, using H9c2 rat cardiomyoblasts, was designed to determine the effects of Sanggenon C on cardiomyocyte hypoxia injury. Inflammatory cytokine levels were measured by reverse transcription‑polymerase chain reaction, reactive oxygen species were measured by 2',7'‑dichlorofluorescin diacetate fluorescent probe, autophagy was detected using the LC3II/I ratio and cell apoptosis was detected by TUNEL staining...
December 2017: Molecular Medicine Reports
Ping Li, Xiaofang Li, Yonghong Wu, Manxiang Li, Xiaochuang Wang
Here, we found that hernandezine, a novel AMPK activator, inhibited LPS-induced TNFα expression/production in human macrophage cells (THP-1 and U937 lines). Activation of AMPK is required for hernandezine-induced anti-LPS response. AMPKα shRNA or dominant negative mutation (T172A) blocked hernandezine-induced AMPK activation, which almost completely reversed anti-LPS activity by hernandezine. Exogenous expression of the constitutively activate AMPKα (T172D, caAMPKα) also suppressed TNFα production by LPS...
September 15, 2017: Oncotarget
Akihiro Nakanishi, Naoya Hatano, Yuya Fujiwara, Arian Bin Shari, Shota Takabatake, Hiroki Akano, Naoki Kanayama, Masaki Magari, Naohito Nozaki, Hiroshi Tokumitsu
The Ca(2+)/calmodulin-dependent protein kinase kinase β(CaMKKβ)/5'AMP-activated protein kinase (AMPK) phosphorylation cascade affects various Ca(2+)-dependent metabolic pathways and cancer growth. Unlike recombinant CaMKKβ that exhibits higher basal activity (autonomous activity), activation of the CaMKKβ/AMPK signaling pathway requires increased intracellular Ca(2+) concentrations. Moreover, the Ca(2+)/CaM dependence of CaMKKβ appears to arise from multiple phosphorylation events, including autophosphorylation and activities furnished by other protein kinases...
October 3, 2017: Journal of Biological Chemistry
Anne-Clemence Vion, Marouane Kheloufi, Adel Hammoutene, Johanne Poisson, Juliette Lasselin, Cecile Devue, Isabelle Pic, Nicolas Dupont, Johanna Busse, Konstantin Stark, Julie Lafaurie-Janvore, Abdul I Barakat, Xavier Loyer, Michele Souyri, Benoit Viollet, Pierre Julia, Alain Tedgui, Patrice Codogno, Chantal M Boulanger, Pierre-Emmanuel Rautou
It has been known for some time that atherosclerotic lesions preferentially develop in areas exposed to low SS and are characterized by a proinflammatory, apoptotic, and senescent endothelial phenotype. Conversely, areas exposed to high SS are protected from plaque development, but the mechanisms have remained elusive. Autophagy is a protective mechanism that allows recycling of defective organelles and proteins to maintain cellular homeostasis. We aimed to understand the role of endothelial autophagy in the atheroprotective effect of high SS...
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
X Zheng, J Chi, J Zhi, H Zhang, D Yue, J Zhao, D Li, Y Li, M Gao, J Guo
Deletion or loss-of-function mutation of LKB1, frequently occurring in non-small cell lung cancers (NSCLCs), is a predominant caution of NSCLC initiation and progression. However, the upstream signaling pathways governing LKB1 activation are largely unknown. Here, we report that LKB1 undergoes Aurora kinase A (AURKA)-mediated phosphorylation, which largely compromises the LKB1/AMPK signaling axis, in turn leading to the elevation of NSCLC cell proliferation, invasion and migration. Mechanically, AURKA-mediated phosphorylation of LKB1 impairs LKB1 interaction with and phosphorylation of its downstream target AMPKα, which has critical roles in governing cancer cell energy metabolic homeostasis and tumorigenesis...
October 2, 2017: Oncogene
So Youn Park, Sung Won Lee, Sang Yeob Lee, Ki Whan Hong, Sun Sik Bae, Koanhoi Kim, Chi Dae Kim
Macrophages are crucially involved in the pathogenesis of rheumatoid arthritis (RA). Macrophages of the M1 phenotype act as pro-inflammatory mediators in synovium, whereas those of the M2 phenotype suppress inflammation and promote tissue repair. SIRT1 is a class 3 histone deacetylase with anti-inflammatory characteristics. However, the role played by SIRT1 in macrophage polarization has not been defined in RA. We investigated whether SIRT1 exerts anti-inflammatory effects by modulating M1/M2 polarization in macrophages from RA patients...
2017: Frontiers in Immunology
Renyan Li, Xue Luo, Yijian Zhu, Letian Zhao, Lianbing Li, Qiang Peng, Mingfu Ma, Yanfei Gao
Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the exact mechanism and role of autophagy induced by Cd in spermatozoa cells. Mouse spermatocyte-derived cells (GC-2) were treated with 20 μM Cd chloride for 24 h. The level of reactive oxygen species (ROS), DNA damage, autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase (AMPK)/mTOR were determined...
December 2017: Environmental Pollution
Limei Piao, Guangxian Zhao, Enbo Zhu, Aiko Inoue, Rei Shibata, Yanna Lei, Lina Hu, Chenglin Yu, Guang Yang, Hongxian Wu, Wenhu Xu, Kenji Okumura, Noriyuki Ouchi, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase-4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon-like peptide-1 (GLP-1) metabolism, we investigated the role of DPP4/GLP-1 axis in vascular senescence and ischemia-induced neovascularization in mice under chronic stress, with a special focus on adiponectin -mediated peroxisome proliferator activated receptor-γ/its co-activator 1α (PGC-1α) activation...
September 28, 2017: Journal of the American Heart Association
Chun-Ping Wan, Ya-Gai Wei, Xiao-Xue Li, Li-Jun Zhang, Rui Yang, Zhao-Ri-Ge-Tu Bao
To investigate the effect of piperine on the disorder of glucose metabolism in the cell model with insulin resistance (IR) and explore the molecules mechanism on intervening the upstream target of AMPK signaling pathway. The insulin resistance models in HepG2 cells were established by fat emulsion stimulation. Then glucose consumption in culture supernatant was detected by GOD-POD method. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of leptin(LEP) and adiponectin(APN) in culture supernatant; Real-time quantitative PCR was used to assess the mRNA expression of APN and LEP; and the protein expression levels of LepR, AdipoR1, AdipoR2 and the activation of AMPK signaling pathway were detected by Western blot analysis...
February 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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