ࡱ>  -bjbjߍ $$t;:\v:x:x:x:x:x:x:G=?x:-x::v:v:M:*:0:o@o@ y:   Supplemental Data Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice Ryan S. Streeper1,3*, Carrie A. Grueter1*, Nathan Salomonis1, Sylvaine Cases1, Malin C. Levin1, Suneil K. Koliwad1,3,4, Ping Zhou1, Matthew D. Hirschey2, Eric Verdin2,4, and Robert V. Farese, Jr.1,3,4,5, 1Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA 2Gladstone Institute of Virology and Immunology, San Francisco, California, USA 3Cardiovascular Research Institute, San Francisco, California, USA 4Department of Medicine, University of California, San Francisco, California, USA 5Departments of Biochemistry and Biophysics, University of California, San Francisco, California, USA *These authors contributed equally. This supplement contains: Supplemental Figures 1-4 Supplemental Table 1 Supplemental Figure Legends  Supplemental Figure 1. Changes in bone mineral density, bone mineral content and leptin levels in middle-aged Dgat1/ mice. (A) Bone mineral density and (B) bone mineral content are lower in middle-aged Dgat1-/- versus WT mice. (C) Serum leptin levels are lower in middle-aged female mice [*p < 0.05 vs. wild-type (WT); n = 8 13].  Young and  Middle-aged refer to ages 3 4 mo and 14 16 mo, respectively.  Supplemental Figure 2. Similar glucose tolerance and hepatic mitochondrial content in middle-aged WT and Dgat1/ mice. (A) Blood glucose levels of middle-aged mice before and after an intraperitoneal injection of glucose (1 mg/g body weight). Mice were fed regular chow and fasted 56 hours before the test. (B) Mitochondrial (mt) DNA content and (C) citrate synthase (CS) activity, a marker of mitochondrial activity, from the livers of middle-aged mice (n=4 and 10, respectively).  Supplemental Figure 3. Validation of microarray anlaysis with qRT-PCR. Differentially expressed genes in the livers of WTCR and Dgat1/ AL vs. WT ad libitum mice. Values are mean SEM of biological triplicates.  Supplemental Figure 4. Analysis of cholesterol biosynthesis pathway. Cholesterol biosynthesis pathway-highlighted genes (WikiPathways: WP103, revision 41337) that are significantly down-regulated in WTCR (left) or KOAL (right) relative to WTAL based on pathway analysis from the program GenMAPP-CS. Supplemental Table 1. A. Genes commonly up-regulated in liver of short-term calorie restricted wild-type (WTCR) and ad libitum Dgat1/ (KOAL) middle-aged (15-16 mo) female mice. ProbeSetIDGeneSymbolfold.WTCR-WTALfold.KOAL-WTALrawP.WTCR-WTALrawP.KOAL-WTAL10349431Acmsd1.512.152.4E-028.0E-0410488608Trib31.831.784.8E-036.2E-0310496077Agxt2l11.951.783.8E-041.0E-0310593937Mpi1.521.479.5E-031.4E-0210589099Ihpk21.721.448.8E-049.2E-03105196074930420K17Rik1.421.432.2E-032.1E-0310503023Cth1.311.439.8E-032.1E-0310441359---1.491.426.4E-031.3E-0210368947Aim12.041.395.0E-057.6E-0310571891Aadat1.691.393.3E-033.3E-0210399430Ddx11.371.381.2E-021.2E-0210464754Rhod1.961.377.6E-044.3E-0210378568---1.581.371.0E-039.4E-0310434289---1.551.361.2E-041.4E-0310574641D230025D16Rik1.521.362.4E-031.4E-0210585823LOC6652681.361.353.0E-033.5E-0310593671Dmxl21.751.347.0E-042.4E-0210515187Cyp4a142.601.342.9E-054.0E-0210409021Tpmt1.341.333.1E-033.4E-0310357878Adora11.601.332.0E-032.9E-0210354233Tgfbrap11.321.334.5E-024.1E-0210581340Ranbp101.341.322.3E-023.0E-0210398195Ccnk1.321.321.3E-021.3E-0210593668Dmxl21.541.314.6E-034.0E-0210410124Ctsl1.481.312.5E-031.7E-0210475247Tmem621.351.312.7E-023.8E-0210436200EG6678021.441.311.3E-024.9E-0210485622Qser11.341.316.3E-039.9E-03104202162310014G06Rik1.601.311.3E-045.0E-03 B. Genes commonly down-regulated in liver of short-term calorie restricted wild-type (WTCR) and ad libitum Dgat1-/- (KOAL) middle-aged (15-16 mo) female mice. ProbeSetIDGeneSymbolfold.WTCR-WTALfold.KOAL-WTALrawP.WTCR-WTALrawP.KOAL-WTAL10531126Igj-5.01-2.861.1E-031.3E-0210523359Cxcl13-2.80-2.522.6E-024.1E-0210585699ENSMUST00000098689-3.58-2.261.9E-043.7E-0310509163Id3-2.29-2.198.3E-041.2E-0310490838Fabp5-3.41-2.144.2E-048.0E-0310425161Lgals1-1.62-2.004.5E-028.9E-0310361246G0s2-2.51-1.951.6E-041.4E-0310425822Pnpla3-1.99-1.943.2E-023.8E-0210603860Cfp-1.50-1.874.3E-025.5E-0310587082Onecut1-1.69-1.821.5E-036.1E-0410446282Emr1-2.19-1.802.7E-031.3E-0210365830----1.53-1.772.2E-025.0E-0310582310Mvd-1.95-1.775.3E-041.5E-0310402347Ifi27-1.94-1.732.9E-041.1E-0310407281Esm1-1.53-1.721.7E-033.3E-0410571321Ppp1r3b-1.43-1.692.3E-023.1E-0310385504EG432555-1.91-1.692.5E-041.0E-0310438405Igl-V1 /// Igl-J2 /// Igl-V2 /// LOC433053-1.88-1.669.3E-043.5E-0310501063Cd53-1.59-1.641.0E-027.5E-0310517165Cd52-2.16-1.631.2E-053.4E-0410455015----3.90-1.631.1E-044.2E-0210404606Ly86-1.85-1.612.9E-031.2E-0210461614Ms4a6c-2.76-1.612.8E-055.0E-0310385518Tgtp /// OTTMUSG00000005523-3.25-1.616.6E-051.9E-0210458890----1.41-1.594.1E-036.2E-0410545187EG628498 /// Gm1502 /// Igkv4-74 /// Gm1524 /// LOC100047316-1.93-1.596.9E-045.8E-0310538903ENSMUSG00000076577 /// Igk-V28 /// Igkv6-25 /// Igk-V21-4 /// Igk /// Gm1499 /// LOC676193-2.10-1.594.7E-048.5E-0310466200Ms4a7-1.69-1.587.9E-031.6E-0210499483Fdps-1.39-1.583.0E-026.1E-0310403034Igh /// LOC676399 /// LOC100046275-1.74-1.571.4E-023.5E-0210385533Tgtp /// OTTMUSG00000005523-2.81-1.563.2E-043.5E-0210603551Cybb-1.82-1.562.9E-031.4E-0210444258Psmb8-2.08-1.561.1E-043.1E-0310403063Igh /// LOC100046275 /// LOC676399-1.57-1.541.1E-021.4E-0210368240Tcf21-1.40-1.531.3E-023.7E-0310517517C1qa-1.45-1.531.9E-029.6E-0310545237----1.37-1.536.3E-031.1E-0310403743Inhba-1.42-1.522.2E-037.1E-0410531724Plac8-2.20-1.521.6E-034.0E-0210444291H2-Ab1 /// Rmcs5 /// Rmcs2-3.02-1.528.5E-066.9E-0310450154H2-Aa-3.57-1.522.1E-052.4E-0210545198EG667683 /// Igk /// Gm1499 /// Gm1524-1.79-1.512.3E-031.5E-0210545184EG628498 /// Igkv4-74 /// Gm189 /// Gm1524 /// LOC100047316-2.02-1.512.7E-047.8E-0310503359C430048L16Rik-1.67-1.504.4E-042.2E-0310412466Hmgcs1-2.41-1.491.6E-041.8E-0210496592Gbp2-2.00-1.492.1E-033.5E-0210545196Igk-C /// Gm1524 /// Igk /// Gm1499 /// Gm1418 /// Gm189 /// Igkv4-74-1.57-1.491.5E-043.7E-0410379630Slfn2-1.89-1.497.0E-051.8E-0310556018----1.49-1.481.8E-021.9E-0210576774Clec4g-2.00-1.481.7E-051.1E-0310389231Ccl3-1.38-1.471.5E-026.0E-0310539433Mobkl1b-1.59-1.471.3E-023.1E-0210559467Pira11 /// Pira6 /// Pira4 /// Pira3 /// Pira7 /// OTTMUSG00000022068 /// Pira2 /// Lilrb3-1.66-1.453.4E-042.5E-0310582303Cyba-1.46-1.451.0E-021.0E-0210389207Ccl5-1.89-1.451.7E-032.9E-0210466606Anxa1-1.35-1.453.3E-021.3E-0210424349Sqle-1.35-1.442.0E-028.3E-0310568024Coro1a-1.62-1.416.2E-044.7E-0310401181Rdh11-1.69-1.412.0E-031.9E-0210607865Tmsb4x-2.23-1.412.4E-057.2E-0310545731Clec4f-1.69-1.415.6E-047.3E-0310569646Ccnd1-4.08-1.412.0E-062.4E-0210421648Slc25a30-2.16-1.401.8E-042.5E-0210545202Gm1077 /// Gm1418-1.39-1.391.6E-021.6E-0210555087----1.37-1.391.3E-021.0E-0210420730Fdft1-1.32-1.392.9E-021.3E-0210360382Ifi204 /// Mnda /// Ifi205-2.45-1.381.1E-044.3E-0210503995Dnaja1-1.81-1.381.8E-034.3E-0210358224Ptprc-2.43-1.375.8E-053.0E-0210444298H2-Eb1-2.43-1.361.1E-044.7E-0210539135Capg-1.35-1.356.2E-035.9E-0310367050Rdh18-1.31-1.353.3E-022.1E-0210473125Itga4 /// Cerkl-1.52-1.358.7E-046.5E-0310480699Dpp7-1.65-1.352.0E-045.3E-0310569102Irf7-1.56-1.356.6E-034.0E-0210548892Arhgdib-1.53-1.357.7E-046.8E-0310356020Dock10-1.94-1.346.3E-073.2E-0410531952Abcg3-1.87-1.345.4E-043.4E-02104122072310016C16Rik-1.44-1.347.4E-032.1E-02103666401190005P17Rik-1.35-1.348.2E-039.0E-0310385513EG432555 /// 9930111J21Rik /// Psme2b-ps /// RP23-269N23.3-1.91-1.344.0E-058.0E-0310367066Rdh20-3.46-1.321.7E-063.2E-0210563441Emp3-1.41-1.324.5E-031.4E-0210524621Oasl2-1.55-1.327.4E-041.1E-0210603573Sytl5-1.91-1.321.8E-056.2E-03103956126030408C04Rik-1.35-1.311.4E-022.2E-0210466210Ms4a6d-1.37-1.312.8E-036.9E-0310500335Fcgr1-1.43-1.319.0E-033.4E-0210403079LOC435333-1.51-1.305.2E-047.9E-0310530910Uba6-1.77-1.306.3E-044.1E-02 Supplementary Table 2. Primers used for quantitative RT-PCR analysis. 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