|
|
char = I;code = 73
char = n;code = 110
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char = i;code = 105
char = n;code = 110
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char = t;code = 116
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char = i;code = 105
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char = c;code = 99
char = a;code = 97
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char = e;code = 101
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char = i;code = 105
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char = s;code = 115
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
result sql = Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dysfunction in diet-induced obesity.
Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dysfunction in diet-induced obesity.char = <;code = 60
char = b;code = 98
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char = B;code = 66
char = A;code = 65
char = C;code = 67
char = K;code = 75
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char = N;code = 78
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char = :;code = 58
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char = T;code = 84
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char = <;code = 60
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char = <;code = 60
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char = H;code = 72
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char = A;code = 65
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char = R;code = 82
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char = L;code = 76
char = T;code = 84
char = S;code = 83
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char = ;code = 32
char = <;code = 60
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char = 1;code = 49
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char = s;code = 115
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char = 2;code = 50
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char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = h;code = 104
char = i;code = 105
char = g;code = 103
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char = a;code = 97
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char = d;code = 100
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char = e;code = 101
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char = a;code = 97
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char = l;code = 108
char = e;code = 101
char = d;code = 100
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char = t;code = 116
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char = u;code = 117
char = p;code = 112
char = r;code = 114
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char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = y;code = 121
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char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
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char = o;code = 111
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char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = s;code = 115
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char = G;code = 71
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = 5;code = 53
char = 1;code = 49
char = %;code = 37
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = 3;code = 51
char = -;code = 45
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = A;code = 65
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
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char = e;code = 101
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char = (;code = 40
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = 6;code = 54
char = 7;code = 55
char = %;code = 37
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = -;code = 45
char = C;code = 67
char = o;code = 111
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = 4;code = 52
char = -;code = 45
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = d;code = 100
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = r;code = 114
char = e;code = 101
char = m;code = 109
char = o;code = 111
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char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = o;code = 111
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char = i;code = 105
char = c;code = 99
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char = e;code = 101
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
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char = t;code = 116
char = o;code = 111
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char = f;code = 102
char = a;code = 97
char = v;code = 118
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = h;code = 104
char = i;code = 105
char = f;code = 102
char = t;code = 116
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char = o;code = 111
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char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = c;code = 99
char = e;code = 101
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char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = n;code = 110
char = o;code = 111
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char = m;code = 109
char = a;code = 97
char = l;code = 108
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char = d;code = 100
char = i;code = 105
char = e;code = 101
char = t;code = 116
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char = m;code = 109
char = a;code = 97
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char = n;code = 110
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char = a;code = 97
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char = n;code = 110
char = e;code = 101
char = d;code = 100
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char = o;code = 111
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char = a;code = 97
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char = ;code = 32
char = c;code = 99
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char = i;code = 105
char = a;code = 97
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char = n;code = 110
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char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = f;code = 102
char = u;code = 117
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char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = i;code = 105
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char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = t;code = 116
char = o;code = 111
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char = u;code = 117
char = p;code = 112
char = r;code = 114
char = e;code = 101
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char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = m;code = 109
char = y;code = 121
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = y;code = 121
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char = a;code = 97
char = c;code = 99
char = i;code = 105
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char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = f;code = 102
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
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char = f;code = 102
char = a;code = 97
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char = i;code = 105
char = e;code = 101
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char = s;code = 115
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char = t;code = 116
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char = n;code = 110
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
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char = o;code = 111
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char = v;code = 118
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char = s;code = 115
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char = e;code = 101
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char = ;code = 32
char = p;code = 112
char = 3;code = 51
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char = p;code = 112
char = r;code = 114
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char = t;code = 116
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char = k;code = 107
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char = a;code = 97
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char = e;code = 101
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char = ;code = 32
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char = a;code = 97
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char = i;code = 105
char = l;code = 108
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char = y;code = 121
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char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
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char = W;code = 87
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
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char = e;code = 101
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char = s;code = 115
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char = a;code = 97
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char = a;code = 97
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char = o;code = 111
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = i;code = 105
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char = m;code = 109
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char = o;code = 111
char = c;code = 99
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char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = g;code = 103
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char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
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char = u;code = 117
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
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char = a;code = 97
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char = d;code = 100
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char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = r;code = 114
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
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char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = i;code = 105
char = b;code = 98
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result sql = BACKGROUND : Shift of myocardial substrate preference has been observed in many chronic diseases such as diabetes and heart failure. This study was undertaken to elucidate the mechanisms underlying the chronic substrate switch in adult hearts and to determine the functional consequences of the switch.
METHODS AND RESULTS : Transgenic mice with cardiac-specific overexpression of the insulin-independent glucose transporter GLUT1 (TG) were used to increase intracellular glucose in cardiac myocytes. A high-fat diet was used to increase the fatty acid supply to the heart. High-fat diet induced a 40% increase in fatty acid oxidation in wild-type hearts, whereas glucose oxidation was decreased to 30% of the control. In contrast, glucose oxidation was >2-fold higher in TG hearts, and the high-fat diet failed to upregulate fatty acid oxidation in these hearts. Glucose induced changes in the expression of multiple metabolic genes, including peroxisome proliferator-activated receptor-alpha (decreased by 51%), 3-oxoacid CoA transferase (decreased by 67%), and acetyl-CoA carboxylase (increased by 4-fold), resulting in a remodeling of the metabolic network to favor a shift of substrate preference toward glucose. Although TG mice on a normal diet maintained normal cardiac energetics and function, the inability to upregulate myocardial fatty acid oxidation in TG mice fed a high-fat diet resulted in increased oxidative stress in the heart, activation of p38 mitogen-activated protein kinase, and contractile dysfunction.
CONCLUSIONS : We have demonstrated that chronic increases in myocardial glucose uptake and oxidation reduce the metabolic flexibility and render the heart susceptible to contractile dysfunction.
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result sql = Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dysfunction in diet-induced obesity.
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char = s;code = 115
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char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = d;code = 100
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = t;code = 116
char = o;code = 111
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char = 3;code = 51
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char = %;code = 37
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
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char = e;code = 101
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char = c;code = 99
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char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
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char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = >;code = 62
char = 2;code = 50
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char = f;code = 102
char = o;code = 111
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char = h;code = 104
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char = g;code = 103
char = h;code = 104
char = e;code = 101
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
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char = a;code = 97
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char = d;code = 100
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char = e;code = 101
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char = f;code = 102
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = y;code = 121
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char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
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char = o;code = 111
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char = i;code = 105
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = G;code = 71
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
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char = x;code = 120
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
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char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = (;code = 40
char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = 5;code = 53
char = 1;code = 49
char = %;code = 37
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = 3;code = 51
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char = o;code = 111
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char = o;code = 111
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = A;code = 65
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char = t;code = 116
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char = a;code = 97
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char = s;code = 115
char = f;code = 102
char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = d;code = 100
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char = c;code = 99
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char = a;code = 97
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char = 7;code = 55
char = %;code = 37
char = );code = 41
char = ,;code = 44
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
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char = y;code = 121
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char = -;code = 45
char = C;code = 67
char = o;code = 111
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = o;code = 111
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char = l;code = 108
char = a;code = 97
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char = e;code = 101
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
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char = b;code = 98
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char = 4;code = 52
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char = o;code = 111
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char = d;code = 100
char = );code = 41
char = ,;code = 44
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char = r;code = 114
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char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = m;code = 109
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char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = o;code = 111
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char = i;code = 105
char = c;code = 99
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char = e;code = 101
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
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char = t;code = 116
char = o;code = 111
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char = f;code = 102
char = a;code = 97
char = v;code = 118
char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = h;code = 104
char = i;code = 105
char = f;code = 102
char = t;code = 116
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char = o;code = 111
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char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = c;code = 99
char = e;code = 101
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char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = t;code = 116
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char = m;code = 109
char = a;code = 97
char = i;code = 105
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char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
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char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
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char = r;code = 114
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = c;code = 99
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char = e;code = 101
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char = e;code = 101
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = f;code = 102
char = u;code = 117
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char = c;code = 99
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char = i;code = 105
char = o;code = 111
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char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
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char = i;code = 105
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char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = t;code = 116
char = o;code = 111
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char = u;code = 117
char = p;code = 112
char = r;code = 114
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char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = a;code = 97
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char = t;code = 116
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char = o;code = 111
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char = n;code = 110
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char = T;code = 84
char = G;code = 71
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = f;code = 102
char = e;code = 101
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char = a;code = 97
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char = h;code = 104
char = i;code = 105
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char = h;code = 104
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char = f;code = 102
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
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char = o;code = 111
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char = a;code = 97
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char = v;code = 118
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char = h;code = 104
char = e;code = 101
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char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = v;code = 118
char = a;code = 97
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
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char = m;code = 109
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char = t;code = 116
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char = n;code = 110
char = -;code = 45
char = a;code = 97
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char = t;code = 116
char = i;code = 105
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
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char = k;code = 107
char = i;code = 105
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char = a;code = 97
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char = e;code = 101
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = y;code = 121
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char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
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result sql = BACKGROUND : Shift of myocardial substrate preference has been observed in many chronic diseases such as diabetes and heart failure. This study was undertaken to elucidate the mechanisms underlying the chronic substrate switch in adult hearts and to determine the functional consequences of the switch.
METHODS AND RESULTS : Transgenic mice with cardiac-specific overexpression of the insulin-independent glucose transporter GLUT1 (TG) were used to increase intracellular glucose in cardiac myocytes. A high-fat diet was used to increase the fatty acid supply to the heart. High-fat diet induced a 40% increase in fatty acid oxidation in wild-type hearts, whereas glucose oxidation was decreased to 30% of the control. In contrast, glucose oxidation was >2-fold higher in TG hearts, and the high-fat diet failed to upregulate fatty acid oxidation in these hearts. Glucose induced changes in the expression of multiple metabolic genes, including peroxisome proliferator-activated receptor-alpha (decreased by 51%), 3-oxoacid CoA transferase (decreased by 67%), and acetyl-CoA carboxylase (increased by 4-fold), resulting in a remodeling of the metabolic network to favor a shift of substrate preference toward glucose. Although TG mice on a normal diet maintained normal cardiac energetics and function, the inability to upregulate myocardial fatty acid oxidation in TG mice fed a high-fat diet resulted in increased oxidative stress in the heart, activation of p38 mitogen-activated protein kinase, and contractile dysfunction.
CONCLUSIONS : We have demonstrated that chronic increases in myocardial glucose uptake and oxidation reduce the metabolic flexibility and render the heart susceptible to contractile dysfunction.
Publication: Circulation 2009 Jun 2 ;119(21)::2818-28. :doi: 10.1161/CIRCULATIONAHA.108.832915.
Publication Date: 2009 Jun 2
Study Author(s): Yan, Jie;Young, Martin E;Cui, Lei;Lopaschuk, Gary D;Liao, Ronglih;Tian, Rong;
Institution: Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shortcut link to this study:
Publication Date: 2009 Jun 2
Study Author(s): Yan, Jie;Young, Martin E;Cui, Lei;Lopaschuk, Gary D;Liao, Ronglih;Tian, Rong;
Institution: Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shortcut link to this study:
BACKGROUND : Shift of myocardial substrate preference has been observed in many chronic diseases such as diabetes and heart failure. This study was undertaken to elucidate the mechanisms underlying the chronic substrate switch in adult hearts and to determine the functional consequences of the switch.
METHODS AND RESULTS : Transgenic mice with cardiac-specific overexpression of the insulin-independent glucose transporter GLUT1 (TG) were used to increase intracellular glucose in cardiac myocytes. A high-fat diet was used to increase the fatty acid supply to the heart. High-fat diet induced a 40% increase in fatty acid oxidation in wild-type hearts, whereas glucose oxidation was decreased to 30% of the control. In contrast, glucose oxidation was >2-fold higher in TG hearts, and the high-fat diet failed to upregulate fatty acid oxidation in these hearts. Glucose induced changes in the expression of multiple metabolic genes, including peroxisome proliferator-activated receptor-alpha (decreased by 51%), 3-oxoacid CoA transferase (decreased by 67%), and acetyl-CoA carboxylase (increased by 4-fold), resulting in a remodeling of the metabolic network to favor a shift of substrate preference toward glucose. Although TG mice on a normal diet maintained normal cardiac energetics and function, the inability to upregulate myocardial fatty acid oxidation in TG mice fed a high-fat diet resulted in increased oxidative stress in the heart, activation of p38 mitogen-activated protein kinase, and contractile dysfunction.
CONCLUSIONS : We have demonstrated that chronic increases in myocardial glucose uptake and oxidation reduce the metabolic flexibility and render the heart susceptible to contractile dysfunction.
METHODS AND RESULTS : Transgenic mice with cardiac-specific overexpression of the insulin-independent glucose transporter GLUT1 (TG) were used to increase intracellular glucose in cardiac myocytes. A high-fat diet was used to increase the fatty acid supply to the heart. High-fat diet induced a 40% increase in fatty acid oxidation in wild-type hearts, whereas glucose oxidation was decreased to 30% of the control. In contrast, glucose oxidation was >2-fold higher in TG hearts, and the high-fat diet failed to upregulate fatty acid oxidation in these hearts. Glucose induced changes in the expression of multiple metabolic genes, including peroxisome proliferator-activated receptor-alpha (decreased by 51%), 3-oxoacid CoA transferase (decreased by 67%), and acetyl-CoA carboxylase (increased by 4-fold), resulting in a remodeling of the metabolic network to favor a shift of substrate preference toward glucose. Although TG mice on a normal diet maintained normal cardiac energetics and function, the inability to upregulate myocardial fatty acid oxidation in TG mice fed a high-fat diet resulted in increased oxidative stress in the heart, activation of p38 mitogen-activated protein kinase, and contractile dysfunction.
CONCLUSIONS : We have demonstrated that chronic increases in myocardial glucose uptake and oxidation reduce the metabolic flexibility and render the heart susceptible to contractile dysfunction.
PMID: 19451348
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