SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice
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{"title"=>"SirT1 regulates energy metabolism and response to caloric restriction in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Gino", "last_name"=>"Boily", "scopus_author_id"=>"56743144400"}, {"first_name"=>"Erin L.", "last_name"=>"Seifert", "scopus_author_id"=>"15840392200"}, {"first_name"=>"Lisa", "last_name"=>"Bevilacqua", "scopus_author_id"=>"7005080761"}, {"first_name"=>"Xiao Hong", "last_name"=>"He", "scopus_author_id"=>"24437935600"}, {"first_name"=>"Guillaume", "last_name"=>"Sabourin", "scopus_author_id"=>"24438140400"}, {"first_name"=>"Carmen", "last_name"=>"Estey", "scopus_author_id"=>"24437712000"}, {"first_name"=>"Cynthia", "last_name"=>"Moffat", "scopus_author_id"=>"24438199500"}, {"first_name"=>"Sean", "last_name"=>"Crawford", "scopus_author_id"=>"24437565900"}, {"first_name"=>"Sarah", "last_name"=>"Saliba", "scopus_author_id"=>"24438118700"}, {"first_name"=>"Karen", "last_name"=>"Jardine", "scopus_author_id"=>"6701342712"}, {"first_name"=>"Jian", "last_name"=>"Xuan", "scopus_author_id"=>"36779577900"}, {"first_name"=>"Meredith", "last_name"=>"Evans", "scopus_author_id"=>"35589712200"}, {"first_name"=>"Mary Ellen", "last_name"=>"Harper", "scopus_author_id"=>"7201849148"}, {"first_name"=>"Michael W.", "last_name"=>"McBurney", "scopus_author_id"=>"7005942894"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"45549098657", "pmid"=>"18335035", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"351903300", "issn"=>"19326203", "scopus"=>"2-s2.0-45549098657", "doi"=>"10.1371/journal.pone.0001759"}, "id"=>"52bd6a00-da8b-3d62-b03e-72b34e6fd215", "abstract"=>"The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.", "link"=>"http://www.mendeley.com/research/sirt1-regulates-energy-metabolism-response-caloric-restriction-mice", "reader_count"=>153, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>17, "Researcher"=>34, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>48, "Student > Postgraduate"=>4, "Student > Master"=>17, "Other"=>4, "Student > Bachelor"=>18, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>17, "Researcher"=>34, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>48, "Student > Postgraduate"=>4, "Student > Master"=>17, "Other"=>4, "Student > Bachelor"=>18, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>27, "Medicine and Dentistry"=>18, "Agricultural and Biological Sciences"=>92, "Neuroscience"=>5, "Design"=>1, "Psychology"=>1, "Chemistry"=>3}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>18}, "Neuroscience"=>{"Neuroscience"=>5}, "Chemistry"=>{"Chemistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>92}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>27}, "Unspecified"=>{"Unspecified"=>5}}, "reader_count_by_country"=>{"Argentina"=>1, "South Korea"=>1, "United States"=>7, "Finland"=>1, "Denmark"=>1, "United Kingdom"=>1, "Italy"=>1, "Slovenia"=>1, "Chile"=>1, "Switzerland"=>1, "Germany"=>2, "India"=>1}, "group_count"=>6}

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Figshare

  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/935419/Figure_1.tif"], "description"=>"<p>A. Body weights of sibling animals of normal (SirT1<sup>+/+</sup> and SirT1<sup>+/−</sup>) and SirT1(<sup>−/−</sup>)-null genotypes at 2–4, 5–8 and 13–20 months of age. B. Daily food intake of mice as described in A. C. Daily food intake normalized to body weight. D. Caloric content of feces from 2–4 months old normal and SirT1-null mice. Means and standard errors are represented along with the number of animals used for each determination. Unpaired T-tests were performed to assess statistical significance.</p>", "links"=>[], "tags"=>["mice"], "article_id"=>605849, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_SirT1_null_mice_are_hyperphagic_/605849", "title"=>"SirT1-null mice are hyperphagic.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:50:54"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/935503/Figure_2.tif"], "description"=>"<p>Activity during 60-minute intervals of individually caged SirT1-null and normal littermates 3–6 months (A) and 9–12 months (B) of age. Insets show histograms of total activity in a 24 hour period. Grey and black lines above the X-axis indicate light and dark periods, respectively. Means and standard errors are represented. Unpaired T-tests were performed to assess statistical significance.</p>", "links"=>[], "tags"=>["mice"], "article_id"=>605939, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_SirT1_null_mice_are_less_active_than_controls_/605939", "title"=>"SirT1-null mice are less active than controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:51:26"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/935590/Figure_3.tif"], "description"=>"<p>A. T4 levels were measured from serum samples of SirT1-null and normal mice using an EIA kit. B. Corticosterone levels were measured from plasma samples of SirT1-null and normal mice at 4 hours intervals during the diurnal cycle using an EIA kit. The peak values are plotted. Unpaired T-tests were performed to assess statistical significance. Blood glucose (C) and insulin (D) levels of 2–3 months old mutant and wild type mice were measured after 24 hour fasting and again 3 hours after refeeding using a standard glucometer (C) and an ELISA kit (D). Means and standard errors are represented. Two-way ANOVAs was performed to assess statistical significance of interaction between genotype and dietary condition (p*-values on top of panel), and unpaired T-test to assess difference between genotypes within dietary condition groups (p-value over bars).</p>", "links"=>[], "tags"=>["thyroxin", "glucose", "insulin"], "article_id"=>606023, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Serum_thyroxin_T4_corticosterone_glucose_and_insulin_levels_/606023", "title"=>"Serum thyroxin (T4), corticosterone, glucose and insulin levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:51:53"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/935676/Figure_4.tif"], "description"=>"<p>Whole animal indirect calorimetry (IC) was used to assess oxygen consumption normalized to body weight (VO<sub>2</sub>/BWT) plotted (panel A) at 30 minute intervals during a 24 hour period or (panel B) as the percent relative cumulative frequency (PRCF) of VO<sub>2</sub>/BWT. The respiratory exchange ratio (RER = VO<sub>2</sub>/VCO<sub>2</sub>) was calculated from VO<sub>2</sub> and VCO<sub>2</sub> data and plotted at 30 minute intervals during a 24 hour period (panel C) or as PRCF (panel D). In a fasting-refeeding experiment (panel E), food was either removed or added at the indicated times (arrows) and the interval RER plotted. Grey and black lines above the X-axis (panels A, C, and E) indicate light and dark periods, respectively. An RER of 1.0 is expected for glucose oxidation and an RER of 0.7 occurs during lipid oxidation. Means and standard errors are represented. An unpaired T-test using medians was performed to assess statistical significance (B).</p>", "links"=>[], "tags"=>["mice"], "article_id"=>606106, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_SirT1_null_mice_are_hypermetabolic_/606106", "title"=>"SirT1-null mice are hypermetabolic.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:52:26"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/935757/Figure_5.tif"], "description"=>"<p>Organs from 3–5 month (A–C) and 13–26 month old mice (D–F) were weighed and plotted. Inguinal fat pad (A, D), interscapular BAT (B, E) and brain (C, F) are plotted as means and standard errors. Unpaired T-tests were performed to assess statistical significance.</p>", "links"=>[], "tags"=>["weights", "sirt1-null"], "article_id"=>606196, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Organ_weights_of_SirT1_null_mice_/606196", "title"=>"Organ weights of SirT1-null mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:52:56"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/935855/Figure_6.tif"], "description"=>"<p>A. State 3 oxygen consumption rate of liver mitochondria from SirT1-null and normal mice was determined using succinate, in the presence of rotenone. Proton motive force (PMF) was determined in liver mitochondria (B) using succinate, in the presence of rotenone and a saturating amount of oligomycin. The farthest point on the right represents the maximal state 4 oxygen consumption rates. The kinetic response of PMF was determined by inhibiting respiration targeting complex II by incremental additions of malonate (up to 5 mM). C. Western blot of UCP2 from liver mitochondria. Thirty µg of mitochondria-enriched proteins from normal spleen (Spl., positive control) or liver from 3 different SirT1-null and normal mice were loaded separately in each lane, electrophoresed, blotted and probed with an antibody to UCP2. Note that UCP2 protein expression is not de-repressed in mutants. D–E. ROS production from liver mitochondria was measured using the p-hydroxyphenylacetate (PHPA) assay using the substrates and respiration inhibitors indicated at the top of each column. F. Western blot of phospho-AMPKα (pAMPK), AMPα (AMPK), and α−tubulin. Hundred-fifty µg of liver proteins from 2–3 different SirT1-null and normal mice under the indicated dietary condition was loaded separately in each lane, electrophoresed, blotted and probed with an antibody to pAMPK. Membrane was stripped and reprobed sequentially with antibodies to AMPK and α−tubulin. G. Densitometry of western blot signal in F. Bands in F were quantified by densitometry using the ImageJ software. Means and standard errors are represented. Unpaired (A, G) or paired (D–E) T-tests were performed to assess statistical significance (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001759#s4\" target=\"_blank\">Materials and Methods</a>).</p>", "links"=>[], "tags"=>["ros"], "article_id"=>606287, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Respiration_and_ROS_production_of_isolated_mitochondria_/606287", "title"=>"Respiration and ROS production of isolated mitochondria.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:53:26"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/935952/Figure_7.tif"], "description"=>"<p>The weights of whole body (A), brain (B), inguinal fat pad (C), and interscapular BAT (D) were obtained from 13–15 months old mice, AL-fed or CR for 25 to 28 weeks. Percentages above bars represent the percent reduction in weight compared to AL-fed mice.</p>", "links"=>[], "tags"=>["weights"], "article_id"=>606378, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Whole_body_and_organ_weights_following_CR_/606378", "title"=>"Whole body and organ weights following CR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:54:00"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/936027/Figure_8.tif"], "description"=>"<p>Total activity of normal (A) and SirT1-null (B) mice was monitored using a Micromax system for 24-hour periods at the indicated time after the start of CR. Animals were 5–7 months old at the beginning of CR. Means and standard errors are represented. The activity of CR normal mice increased with time whereas that of AL controls decreased. CR did not alter the activity of SirT1-null mice.</p>", "links"=>[], "tags"=>["mice"], "article_id"=>606461, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Activity_of_mice_during_CR_/606461", "title"=>"Activity of mice during CR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:54:26"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/936087/Figure_9.tif"], "description"=>"<p>Oxygen consumption normalized to whole body weight (VO<sub>2</sub>/BWT) for normal (A, D) and SirT1-null (B, E) mice was measured after 2–4 weeks (A–C) and 21–26 weeks (D–F) of CR or AL diet as indicated. RER from the same animals at 2–4 weeks (C) or 21–26 weeks (F) of CR were also obtained. Data were plotted as PRCF as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001759#pone-0001759-g004\" target=\"_blank\">Figure 4</a>. The normal mice adapted to CR by maintaining their levels of oxygen consumption but the oxygen consumption of SirT1-null animals was higher in AL than in CR. This difference was particularly evident in older SirT1-null mice (panel E) when AL animals' oxygen consumption was very high.</p>", "links"=>[], "tags"=>["molecular biology", "nutrition", "physiology/endocrinology", "physiology/integrative physiology", "physiology/respiratory physiology"], "article_id"=>606517, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Whole_animal_oxygen_consumption_during_CR_/606517", "title"=>"Whole animal oxygen consumption during CR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:54:50"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/936165/Figure_10.tif"], "description"=>"<p>Survival curve for normal (A) and SirT1-null (B) mice that were fed the CR of AL diets. Mutant mice that were euthanized because of eyelid inflammation were excluded from this graph. Grey rectangles represent the period when CR started (5 to 7 months old).</p>", "links"=>[], "tags"=>["had", "beneficial", "sirt1-null"], "article_id"=>606597, "categories"=>["Physiology", "Molecular Biology", "Medicine"], "users"=>["Gino Boily", "Erin L. Seifert", "Lisa Bevilacqua", "Xiao Hong He", "Guillaume Sabourin", "Carmen Estey", "Cynthia Moffat", "Sean Crawford", "Sarah Saliba", "Karen Jardine", "Jian Xuan", "Meredith Evans", "Mary-Ellen Harper", "Michael W. McBurney"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0001759.g010"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_CR_had_no_beneficial_effect_on_survival_of_SirT1_null_mice_/606597", "title"=>"CR had no beneficial effect on survival of SirT1-null mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:55:16"}

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Relative Metric

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