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{"title"=>"AMP Activated Protein Kinase Is Indispensable for Myocardial Adaptation to Caloric Restriction in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Kai", "last_name"=>"Chen", "scopus_author_id"=>"57198085959"}, {"first_name"=>"Satoru", "last_name"=>"Kobayashi", "scopus_author_id"=>"55703085200"}, {"first_name"=>"Xianmin", "last_name"=>"Xu", "scopus_author_id"=>"56168009700"}, {"first_name"=>"Benoit", "last_name"=>"Viollet", "scopus_author_id"=>"55332178100"}, {"first_name"=>"Qiangrong", "last_name"=>"Liang", "scopus_author_id"=>"7102360431"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"368544582", "pmid"=>"23527250", "doi"=>"10.1371/journal.pone.0059682", "sgr"=>"84875110092", "scopus"=>"2-s2.0-84875110092"}, "id"=>"8167c40b-7bfd-348e-809f-66944c22d936", "abstract"=>"Caloric restriction (CR) is a robust dietary intervention known to enhance cardiovascular health. AMP activated protein kinase (AMPK) has been suggested to mediate the cardioprotective effects of CR. However, this hypothesis remains to be tested by using definitive loss-of-function animal models. In the present study, we subjected AMPKα2 knockout (KO) mice and their wild type (WT) littermates to a CR regimen that reduces caloric intake by 20%-40% for 4 weeks. CR decreased body weight, heart weight and serum levels of insulin in both WT and KO mice to the same degree, indicating the effectiveness of the CR protocol. CR activated cardiac AMPK signaling in WT mice, but not in AMPKα2 KO mice. Correspondingly, AMPKα2 KO mice had markedly reduced cardiac function during CR as determined by echocardiography and hemodynamic measurements. The compromised cardiac function was associated with increased markers of oxidative stress, endoplasmic reticulum stress and myocyte apoptosis. Mechanistically, CR down-regulated the expression of ATP5g2, a subunit of mitochondrial ATP synthase, and reduced ATP content in AMPKα2 KO hearts, but not in WT hearts. In addition, CR accelerated cardiac autophagic flux in WT mice, but failed to do so in AMPKα2 KO mice. These results demonstrated that without AMPK, CR triggers adverse effects that can lead to cardiac dysfunction, suggesting that AMPK signaling pathway is indispensible for energy homeostasis and myocardial adaptation to CR, a dietary intervention that normally produces beneficial cardiac effects.", "link"=>"http://www.mendeley.com/research/amp-activated-protein-kinase-indispensable-myocardial-adaptation-caloric-restriction-mice", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Other"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Other"=>5}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>5, "Design"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

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• http://doi.org/10.1016/j.anifeedsci.2018.01.009
• http://doi.org/10.1134/S0006297913090034
• http://doi.org/10.3390/ijms19113481
• http://doi.org/10.3389/fphys.2020.00342
• http://doi.org/10.1111/acel.12652
• http://doi.org/10.1007/s00109-019-01841-6
• http://doi.org/10.1161/CIRCRESAHA.117.311082
• http://doi.org/10.1016/j.mad.2018.07.005
• http://doi.org/10.1016/j.bbadis.2014.05.020
• http://doi.org/10.1016/j.cell.2014.11.006
• http://doi.org/10.1161/JAHA.120.016270
• http://doi.org/10.1177/1744806917703111
• http://doi.org/10.1016/j.yjmcc.2013.12.010
• http://doi.org/10.1080/20013078.2020.1783869
• http://doi.org/10.3389/fphys.2020.00515
• http://doi.org/10.1016/j.cpcardiol.2018.08.003
• http://doi.org/10.1016/j.bbadis.2014.04.023

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/991725"], "description"=>"<p>Both AMPK α2 KO mice and C57B/6 WT littermates were either fed ad libitum (AL) or subjected to CR (mice were allocated 20% less food than AL for 2 weeks and 40% less for another 2 weeks). Western blot analysis of cardiac proteins was performed to assess the total protein levels and the phosphorylation states of AMPK α1/2 and β subunits as well as its downstream target acetyl-CoA carboxylase (ACC) and TSC2 (<b>A</b>). Note: the antibodies against AMPKα and p-AMPKα can recognize both α1 and α2 isoforms. Other parameters indicative of the effectiveness of the CR protocol include body weight (BW, <b>B</b>), heart weight (HW, <b>C</b>), HW/BW ratio (<b>D</b>), blood triglycerides (<b>E</b>), and serum levels of insulin (<b>F</b>) and IGF-1 (<b>G</b>). Data areexpressed as mean ± SE and analyzed by two-way ANOVA. Sample sizes were indicated in the bar graphs.</p>", "links"=>[], "tags"=>["cr", "ko", "mice", "wt"], "article_id"=>655582, "categories"=>["Physiology", "Biochemistry"], "users"=>["Kai Chen", "Satoru Kobayashi", "Xianmin Xu", "Benoit Viollet", "Qiangrong Liang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059682.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_General_effects_of_CR_on_AMPK_945_2_KO_mice_and_their_WT_littermates_/655582", "title"=>"General effects of CR on AMPKα2 KO mice and their WT littermates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-20 11:34:16"}
• {"files"=>["https://ndownloader.figshare.com/files/991728"], "description"=>"<p><b>A.</b> Cardiac ATP contents were determined with a colorimetric/fluorometric assay kit (Abcam, San Francisco, CA). Data are expressed as mean ± SE and analyzed by two-way ANOVA. <b>B.</b> Western blot analysis of proteins involved in regulating mitochondrial function and dynamics.</p>", "links"=>[], "tags"=>["atp", "contents", "atp5g2", "reduced", "ko", "mice"], "article_id"=>655585, "categories"=>["Physiology", "Biochemistry"], "users"=>["Kai Chen", "Satoru Kobayashi", "Xianmin Xu", "Benoit Viollet", "Qiangrong Liang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059682.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cardiac_ATP_contents_and_Atp5g2_expression_levels_were_reduced_in_AMPK_945_2_KO_mice_during_CR_/655585", "title"=>"Cardiac ATP contents and Atp5g2 expression levels were reduced in AMPKα2 KO mice during CR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-20 11:34:38"}
• {"files"=>["https://ndownloader.figshare.com/files/991730"], "description"=>"<p>Both AMPKα2 KO and WT mice were subjected to AL or CR feeding as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059682#pone-0059682-g001\" target=\"_blank\">Figure 1</a>. <b>A.</b> Western blot analysis of protein carbonyl groups (upper), nitrotyrosine (middle) and 4-hydroxynonenal (bottom). <b>B.</b> Western blot analysis of proteins involved in ER stress including CHOP, BiP, PDI, PERK, and IRE1α. Data are expressed as mean ± SE (<i>n</i> = 4) and analyzed by two-way ANOVA, *p<0.05; **p<0.01 vs WT-AL group. <b>C.</b> TUNEL labeling. Apoptotic nuclei were stained green, and slides were counter-stained with Alexa fluor 568 conjugated-phalloidin (red) and DAPI (blue). Scale bars are 20 µm. TUNEL positive cells were expressed as mean ± S.E and analyzed by 2-way ANOVA (<i>n</i> = 5). <b>D.</b> DNA laddering. A semiquantitative PCR-based DNA laddering kit was used to assess the degree of apoptosis in the heart.</p>", "links"=>[], "tags"=>["cardiac", "oxidative", "er", "apoptosis"], "article_id"=>655587, "categories"=>["Physiology", "Biochemistry"], "users"=>["Kai Chen", "Satoru Kobayashi", "Xianmin Xu", "Benoit Viollet", "Qiangrong Liang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059682.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Knocking_out_AMPK_945_2_increased_cardiac_oxidative_stress_ER_stress_and_apoptosis_during_CR_/655587", "title"=>"Knocking out AMPKα2 increased cardiac oxidative stress, ER stress and apoptosis during CR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-20 11:35:05"}
• {"files"=>["https://ndownloader.figshare.com/files/991731"], "description"=>"<p><b>A.</b> CR increased LC3-II levels and decreased p62 levels in WT mice, but not in AMPKα2 KO mice. <b>B.</b> CR increased cardiac autophagic flux in WT mice, but not in AMPKα2 KO mice, as shown by the difference of LC3-II protein levels in the absence and presence of bafilomycin A1 (BFA, 3 µmole/kg), an inhibitor of autophagic degradation. BFA was delivered by i.p. injection 30 minutes before animals were sacrificed. <b>C.</b> CR induced the phosphorylation of ULK1 at ser555 in WT mice, but not in AMPKα2 KO mice. Data in A and B were expressed as mean ± SE and analyzed by two-way ANOVA. Sample sizes were indicated in the bar graphs.</p>", "links"=>[], "tags"=>["cr-induced", "autophagy"], "article_id"=>655588, "categories"=>["Physiology", "Biochemistry"], "users"=>["Kai Chen", "Satoru Kobayashi", "Xianmin Xu", "Benoit Viollet", "Qiangrong Liang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059682.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AMPK_945_2_is_essential_for_the_CR_induced_autophagy_in_the_heart_/655588", "title"=>"AMPKα2 is essential for the CR-induced autophagy in the heart.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-20 11:35:34"}
• {"files"=>["https://ndownloader.figshare.com/files/1012970"], "description"=>"<p>HW indicates heart weight; BW, body weight; TL, tibial length; HR, heart rate; LVIDd, left ventricular (LV) internal diameter in diastole;; LVIDs, LV internal diameter in systole; FS, fractional shortening. Data are presented as Mean±SE and analysized by t test.</p>*<p>p<0.05,</p>**<p>p<0.01 vs AL group.</p>", "links"=>[], "tags"=>["gravimetric", "echocardiographic"], "article_id"=>673380, "categories"=>["Physiology", "Biochemistry"], "users"=>["Kai Chen", "Satoru Kobayashi", "Xianmin Xu", "Benoit Viollet", "Qiangrong Liang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059682.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cardiac_gravimetric_and_echocardiographic_data_/673380", "title"=>"Cardiac gravimetric and echocardiographic data.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-19 00:56:20"}
• {"files"=>["https://ndownloader.figshare.com/files/1012991"], "description"=>"<p>LVESD indicates left ventricle (LV) end systolic diameter; LVEDD, LV end diastolic diameter; LVESV, LV end systolic volume; LVEDV, LV end diastolic volume; EF, ejection fraction; FS, fractional shortening; LVSP, LV systolic pressure; LVEDP, LV end diastolic pressure. Data are presented as Mean±SEM and analysized by 2-way ANAVO with the Bonferroni post-tests.</p>*<p>p<0.05,</p>**<p>p<0.01 vs WT-AL;</p>#<p>p<0.05,</p>##<p>p<0.01 vs AMPKα2 KO-AL;</p>$<p>p<0.05,</p>$$<p>p<0.01 vs WT-CR.</p>", "links"=>[], "tags"=>["echocardiographic", "hemodynamics", "wt", "ko", "mice", "caloric"], "article_id"=>673401, "categories"=>["Physiology", "Biochemistry"], "users"=>["Kai Chen", "Satoru Kobayashi", "Xianmin Xu", "Benoit Viollet", "Qiangrong Liang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059682.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cardiac_echocardiographic_and_hemodynamics_data_in_WT_and_AMPK_945_2_KO_mice_with_or_without_caloric_restriction_/673401", "title"=>"Cardiac echocardiographic and hemodynamics data in WT and AMPKα2 KO mice with or without caloric restriction.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-19 00:56:41"}
• {"files"=>["https://ndownloader.figshare.com/files/1013011"], "description"=>"**<p>p<0.01 vs AL group.</p>", "links"=>[], "tags"=>["cr", "serum", "insulin"], "article_id"=>673421, "categories"=>["Physiology", "Biochemistry"], "users"=>["Kai Chen", "Satoru Kobayashi", "Xianmin Xu", "Benoit Viollet", "Qiangrong Liang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059682.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_CR_on_serum_levels_of_insulin_and_IGF_1_/673421", "title"=>"Effects of CR on serum levels of insulin and IGF-1.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-19 00:57:01"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime