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https://www.readbyqxmd.com/read/28107516/liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#1
Clinton M Hasenour, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes...
2017: PloS One
https://www.readbyqxmd.com/read/28096359/%C3%AE-synuclein-binds-and-sequesters-pike-l-into-lewy-bodies-triggering-dopaminergic-cell-death-via-ampk-hyperactivation
#2
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Li He, P Michael Iuvone, Xuebing Cao, Yi E Sun, Lingjing Jin, Keqiang Ye
The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27941154/controlling-skeletal-muscle-cpt-i-malonyl-coa-sensitivity-the-importance-of-ampk-independent-regulation-of-intermediate-filaments-during-exercise
#3
Paula M Miotto, Gregory R Steinberg, Graham P Holloway
The obligatory role of carnitine palmitoyltransferase-I (CPT-I) in mediating mitochondrial lipid transport is well-established, a process attenuated by malonyl-CoA (M-CoA). However, the necessity of reducing M-CoA concentrations to promote lipid oxidation has recently been challenged, suggesting external-regulation on CPT-I. Since previous work in hepatocytes suggest the involvement of the intermediate-filament fraction of the cytoskeleton in regulating CPT-I, we investigated in skeletal muscle if CPT-I sensitivity for M-CoA inhibition could be regulated by the intermediate -filaments, and whether AMP-activated protein kinase (AMPK) could be involved in this process...
December 8, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27939519/13-ethylberberine-reduces-hmgb1-release-through-ampk-activation-in-lps-activated-raw264-7-cells-and-protects-endotoxemic-mice-from-organ-damage
#4
Dong Ung Lee, Young Shin Ko, Hye Jung Kim, Ki Churl Chang
High mobility group box 1 (HMGB1), a highly conserved non-histone DNA-binding protein, plays an important role in the pathogenesis of sepsis. Previously, the authors reported 13-ethylberberine (13-EBR) has anti-inflammatory and antibacterial effects. However, the effect of 13-EBR on HMGB1 release was not investigated. In the present study, it was hypothesized 13-EBR might reduce HMGB1 release by activating AMPK under septic conditions. The results obtained showed 13-EBR significantly reduced HMGB1 release from LPS-activated RAW264...
December 7, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27925195/palmitoleic-acid-improves-metabolic-functions-in-fatty-liver-by-ppar%C3%AE-dependent-ampk-activation
#5
Camila O Souza, Alexandre A S Teixeira, Luana A Biondo, Edson A Lima, Helena A P Batatinha, Jose C Rosa Neto
BACKGROUND: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. OBJECTIVE: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27895577/fus1-ko-mouse-as-a-model-of-oxidative-stress-mediated-sporadic-alzheimer-s-disease-circadian-disruption-and-long-term-spatial-and-olfactory-memory-impairments
#6
Guillermo Coronas-Samano, Keeley L Baker, Winston J T Tan, Alla V Ivanova, Justus V Verhagen
Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27884163/chronic-adiponectin-deficiency-leads-to-alzheimer-s-disease-like-cognitive-impairments-and-pathologies-through-ampk-inactivation-and-cerebral-insulin-resistance-in-aged-mice
#7
Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling Lam, Koon Ho Chan
BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM...
November 25, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27827305/a-new-leptin-mediated-mechanism-for-stimulating-fatty-acid-oxidation-a-pivotal-role-for-sarcolemmal-fat-cd36
#8
Iman Momken, Adrian Chabowski, Ellen Dirkx, Miranda Nabben, Swati S Jain, Jay T McFarlan, Jan F C Glatz, Joost J F P Luiken, Arend Bonen
Leptin stimulates fatty acid oxidation in muscle and heart; but, the mechanism by which these tissues provide additional intracellular fatty acids for their oxidation remains unknown. We examined, in isolated muscle and cardiac myocytes, whether leptin, via AMP-activated protein kinase (AMPK) activation, stimulated fatty acid translocase (FAT/CD36)-mediated fatty acid uptake to enhance fatty acid oxidation. In both mouse skeletal muscle and rat cardiomyocytes, leptin increased fatty acid oxidation, an effect that was blocked when AMPK phosphorylation was inhibited by adenine 9-β-d-arabinofuranoside or Compound C...
January 1, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/27800610/lipocalin-2-ngal-attenuates-autophagy-to-exacerbate-cardiac-apoptosis-induced-by-myocardial-ischemia
#9
Hye Kyoung Sung, Yee Kwan Chan, Meng Han, James Won Suk Jahng, Erfei Song, Danielson Eric, Thorsten Berger, Tak W Mak, Gary Sweeney
Lipocalin-2 (Lcn2; also termed neutrophil gelatinase-associated lipocalin (NGAL)) levels correlate positively with heart failure (HF) yet mechanisms via which Lcn2 contributes to the pathogenesis of HF remian unclear. In this study we used coronary artery ligation surgery to induce ischemia in wild type (wt) mice and this induced a significant increase in myocardial Lcn2. We then compared wt and Lcn2 knockout (KO) mice and observed that wt mice showed greater ischemia-induced caspase-3 activation and DNA damage measured by TUNEL than Lcn2KO mice...
November 1, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27782167/renoprotective-effects-of-metformin-are-independent-of-organic-cation-transporters-1-2-and-amp-activated-protein-kinase-in-the-kidney
#10
Michael Christensen, Jonas B Jensen, Steen Jakobsen, Niels Jessen, Jørgen Frøkiær, Bruce E Kemp, Allison L Marciszyn, Hui Li, Núria M Pastor-Soler, Kenneth R Hallows, Rikke Nørregaard
The type-2 diabetes drug metformin has proven to have protective effects in several renal disease models. Here, we investigated the protective effects in a 3-day unilateral ureteral obstruction (3dUUO) mouse model. Compared with controls, ureteral obstructed animals displayed increased tubular damage and inflammation. Metformin treatment attenuated inflammation, increased the anti-oxidative response and decreased tubular damage. Hepatic metformin uptake depends on the expression of organic cation transporters (OCTs)...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27780848/sucrose-nonfermenting-related-kinase-enzyme-mediated-rho-associated-kinase-signaling-is-responsible-for-cardiac-function
#11
Stephanie M Cossette, Vijesh J Bhute, Xiaoping Bao, Leanne M Harmann, Mark A Horswill, Indranil Sinha, Adam Gastonguay, Shabnam Pooya, Michelle Bordas, Suresh N Kumar, Shama P Mirza, Sean P Palecek, Jennifer L Strande, Ramani Ramchandran
BACKGROUND: Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our laboratory has previously shown that SNRK (sucrose nonfermenting related kinase) enzyme, which belongs to the AMPK (adenosine monophosphate-activated kinase) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure and death by 8 to 10 months...
December 2016: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/27703271/pioglitazone-ameliorates-smooth-muscle-cell-proliferation-in-cuff-induced-neointimal-formation-by-both-adiponectin-dependent-and-independent-pathways
#12
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
https://www.readbyqxmd.com/read/27668984/deletion-of-ampk%C3%AE-1-attenuates-the-anticontractile-effect-of-perivascular-adipose-tissue-pvat-and-reduces-adiponectin-release
#13
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
https://www.readbyqxmd.com/read/27632705/13-methylberberine-reduces-hmgb1-release-in-lps-activated-raw264-7-cells-and-increases-the-survival-of-septic-mice-through-ampk-p38-mapk-activation
#14
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...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27618008/physiological-and-pathogenic-roles-of-prolyl-isomerase-pin1-in-metabolic-regulations-via-multiple-signal-transduction-pathway-modulations
#15
REVIEW
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...
September 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27611972/activation-of-cannabinoid-receptor-2-ameliorates-dss-induced-colitis-through-inhibiting-nlrp3-inflammasome-in-macrophages
#16
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
https://www.readbyqxmd.com/read/27555298/loss-of-ctrp1-disrupts-glucose-and-lipid-homeostasis
#17
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
https://www.readbyqxmd.com/read/27478876/metformin-improves-urine-concentration-in-rodents-with-nephrogenic-diabetes-insipidus
#18
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
https://www.readbyqxmd.com/read/27467571/metformin-prevents-nigrostriatal-dopamine-degeneration-independent-of-ampk-activation-in-dopamine-neurons
#19
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
https://www.readbyqxmd.com/read/27461402/lkb1-controls-brown-adipose-tissue-growth-and-thermogenesis-by-regulating-the-intracellular-localization-of-crtc3
#20
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...
July 27, 2016: Nature Communications
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