Metabolite Profiling Identifies Pathways Associated With Metabolic Risk in Humans

DOI Web Site 被引用文献17件
  • Susan Cheng
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Eugene P. Rhee
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Martin G. Larson
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Gregory D. Lewis
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Elizabeth L. McCabe
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Dongxiao Shen
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Melinda J. Palma
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Lee D. Roberts
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Andre Dejam
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Amanda L. Souza
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Amy A. Deik
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Martin Magnusson
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Caroline S. Fox
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Christopher J. O'Donnell
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Ramachandran S. Vasan
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Olle Melander
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Clary B. Clish
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Robert E. Gerszten
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...
  • Thomas J. Wang
    From the Framingham Heart Study of the National Heart, Lung and Blood Institute and Boston University School of Medicine, Framingham, MA (S.C., M.G.L., E.L.M., C.S.F., C.J.O., R.S.V., T.J.W.); Cardiology Division (S.C., G.D.L., E.L.M., D.S., M.J.P.. L.D.R., A.D., C.J.O., R.E.G., T.J.W.), Cardiovascular Research Center (R.E.G., T.J.W.), Cardiovascular Research Center (E.P.R., G.D.L., R.E.G.), and Renal Division (E.P.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Division of...

説明

<jats:sec> <jats:title>Background—</jats:title> <jats:p>Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmö Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, −0.04 to −0.22 per 1-SD change in log-glutamine; <jats:italic>P</jats:italic> <0.001), glutamate (0.05 to 0.14; <jats:italic>P</jats:italic> <0.001), and the glutamine-to-glutamate ratio (−0.05 to −0.20; <jats:italic>P</jats:italic> <0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-to-glutamate ratio was associated with lower risk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted <jats:italic>P</jats:italic> =0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance ( <jats:italic>P</jats:italic> =0.01) and decreased blood pressure ( <jats:italic>P</jats:italic> <0.05). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice.</jats:p> </jats:sec>

収録刊行物

  • Circulation

    Circulation 125 (18), 2222-2231, 2012-05-08

    Ovid Technologies (Wolters Kluwer Health)

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