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result sql = Stimulation of cardiac fatty acid oxidation by leptin is mediated by a nitric oxide-p38 MAPK-dependent mechanism.
Stimulation of cardiac fatty acid oxidation by leptin is mediated by a nitric oxide-p38 MAPK-dependent mechanism.
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char = s;code = 115
char = m;code = 109
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
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
char = n;code = 110
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = A;code = 65
char = M;code = 77
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = p;code = 112
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = y;code = 121
char = l;code = 108
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
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = /;code = 47
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
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
char = n;code = 110
char = ,;code = 44
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 = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = f;code = 102
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = t;code = 116
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 = i;code = 105
char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
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
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
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 = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = c;code = 99
char = ;code = 32
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
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
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 = 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 = S;code = 83
char = T;code = 84
char = A;code = 65
char = T;code = 84
char = -;code = 45
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = 3;code = 51
char = 8;code = 56
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
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
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = /;code = 47
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = e;code = 101
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char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;;code = 59
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = o;code = 111
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char = ;code = 32
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
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = o;code = 111
char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
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 = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = o;code = 111
char = n;code = 110
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
char = d;code = 100
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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
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = N;code = 78
char = A;code = 65
char = M;code = 77
char = E;code = 69
char = ,;code = 44
char = ;code = 32
char = B;code = 66
char = 2;code = 50
char = 0;code = 48
char = 2;code = 50
char = 1;code = 49
char = 9;code = 57
char = 0;code = 48
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = A;code = 65
char = G;code = 71
char = 4;code = 52
char = 9;code = 57
char = 0;code = 48
char = .;code = 46
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 = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = N;code = 78
char = A;code = 65
char = M;code = 77
char = E;code = 69
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
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char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = /;code = 47
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = y;code = 121
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char = a;code = 97
char = t;code = 116
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
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char = 8;code = 56
char = ,;code = 44
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char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = ;code = 32
char = S;code = 83
char = B;code = 66
char = 2;code = 50
char = 0;code = 48
char = 2;code = 50
char = 1;code = 49
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char = a;code = 97
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char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = /;code = 47
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char = i;code = 105
char = t;code = 116
char = r;code = 114
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char = t;code = 116
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = G;code = 71
char = 4;code = 52
char = 9;code = 57
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char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
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char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
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char = e;code = 101
char = d;code = 100
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char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
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char = i;code = 105
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = /;code = 47
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
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char = o;code = 111
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = o;code = 111
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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
char = d;code = 100
char = -;code = 45
char = d;code = 100
char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = t;code = 116
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char = m;code = 109
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char = t;code = 116
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = o;code = 111
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char = d;code = 100
char = r;code = 114
char = i;code = 105
char = a;code = 97
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char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = i;code = 105
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = r;code = 114
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = ,;code = 44
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result sql = Leptin has previously been shown to stimulate fatty acid oxidation independent of AMP-activated protein kinase (AMPK). Nitric oxide and p38 mitogen activated protein kinase (MAPK) are known effectors of leptin signaling. The aim of the present study was to determine whether nitric oxide and p38 MAPK mediate the stimulation of leptin by MAPK. Hearts from male Sprague-Dawley rats were mounted on the isolated perfused working heart in the presence or absence of leptin (1.9 nM), N-Nitro-L-Arginine Methyl Ester (L-NAME) (3 microM), the specific p38 MAPK inhibitor 4-[4-(4-Fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-2-yl] phenol (SB202190, 2 microM) and the specific STAT-3 inhibitor (E)-2-Cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490, 5 microM) for the measurement of substrate metabolism and function AMPK : and carnitine palimitoyltransferase-1 activity, nitrate/nitrite levels, STAT-3 phosphorylation and p38 MAPK phosphorylation were measured. To assess mitochondrial function, hearts were perfused with or without leptin prior to the isolation of mitochondria. Leptin stimulated fatty acid oxidation and decreased cardiac function, associated with the activation of STAT-3 and p38 MAPK and an increase in tissue nitrate/nitrite levels; the effect on function was ameliorated and the effect on fatty acid oxidation was prevented by L-NAME, B202190 and AG490.

L-NAME : lowered tissue nitrate/nitrite levels, and prevented the phosphorylation of p38, whereas SB202190 had no effect on tissue nitrate/nitrite levels. AG490 also lowered tissue nitrate/nitrite levels. Leptin had no effect on fatty acid-dependent mitochondrial respiration or uncoupling activity, but, surprisingly, stimulated pyruvate-dependent mitochondrial respiration. These data indicate that leptin stimulates fatty acid oxidation by a STAT-3-nitric oxide-p38 MAPK-dependent mechanism. The target of the pathway is upstream of the mitochondria.

Publication: Eur. J. Pharmacol. 2009 Sep 1 ;617(1-3)::113-7. :doi: 10.1016/j.ejphar.2009.06.037.
Publication Date: 2009 Sep 1
Study Author(s): Sharma, Vijay;Mustafa, Sally;Patel, Natasha;Wambolt, Richard;Allard, Michael F;McNeill, John H;
Institution: Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Shortcut link to this study:
Leptin has previously been shown to stimulate fatty acid oxidation independent of AMP-activated protein kinase (AMPK). Nitric oxide and p38 mitogen activated protein kinase (MAPK) are known effectors of leptin signaling. The aim of the present study was to determine whether nitric oxide and p38 MAPK mediate the stimulation of leptin by MAPK. Hearts from male Sprague-Dawley rats were mounted on the isolated perfused working heart in the presence or absence of leptin (1.9 nM), N-Nitro-L-Arginine Methyl Ester (L-NAME) (3 microM), the specific p38 MAPK inhibitor 4-[4-(4-Fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-2-yl] phenol (SB202190, 2 microM) and the specific STAT-3 inhibitor (E)-2-Cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490, 5 microM) for the measurement of substrate metabolism and function AMPK : and carnitine palimitoyltransferase-1 activity, nitrate/nitrite levels, STAT-3 phosphorylation and p38 MAPK phosphorylation were measured. To assess mitochondrial function, hearts were perfused with or without leptin prior to the isolation of mitochondria. Leptin stimulated fatty acid oxidation and decreased cardiac function, associated with the activation of STAT-3 and p38 MAPK and an increase in tissue nitrate/nitrite levels; the effect on function was ameliorated and the effect on fatty acid oxidation was prevented by L-NAME, B202190 and AG490.

L-NAME : lowered tissue nitrate/nitrite levels, and prevented the phosphorylation of p38, whereas SB202190 had no effect on tissue nitrate/nitrite levels. AG490 also lowered tissue nitrate/nitrite levels. Leptin had no effect on fatty acid-dependent mitochondrial respiration or uncoupling activity, but, surprisingly, stimulated pyruvate-dependent mitochondrial respiration. These data indicate that leptin stimulates fatty acid oxidation by a STAT-3-nitric oxide-p38 MAPK-dependent mechanism. The target of the pathway is upstream of the mitochondria.
PMID: 19573526

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