The <scp>AMPK</scp> agonist 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation‐associated cachectic muscle wasting

Name: Work Video:
Duration: 3 min 30 s
Derek Hall; Takla Griss; F. Jennifer; Brenda Janice Sánchez; Jason Sadek; Anne Marie K Tremblay; Souad Mubaid; Amr Omer; Rebecca J. Ford; Nathalie Bédard; Arnim Pause; Simon S. Wing; Sergio Di Marco; Gregory R. Steinberg; Russell G. Jones; Imed‐Eddine Gallouzi
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794, 822, 853, 883, 909, 939, 989, 1147], 'Takla': [52, 54, 536, 538, 995], 'Griss': [53, 55, 537, 539], 'Physiology,': [67, 443, 551, 927, 1055], 'Jennifer': [80, 83, 564, 567, 997], 'F': [81, 84, 565, 568, 998], 'Ma': [82, 85, 566, 569], 'Brenda': [110, 113, 594, 597, 1000], 'Janice': [111, 114, 595, 598, 1001], 'Sanchez': [112, 115, 596, 599], 'Jason': [140, 142, 624, 626, 1003], 'Sadek': [141, 143, 625, 627], 'Anne': [168, 172, 652, 656, 1005], 'Marie': [169, 173, 653, 657, 1006], 'K': [170, 174, 654, 658, 1007], 'Tremblay': [171, 175, 655, 659], 'Souad': [200, 202, 684, 686, 1009], 'Mubaid': [201, 203, 685, 687], 'Amr': [228, 230, 712, 714, 1011], 'Omer': [229, 231, 713, 715], 'Rebecca': [256, 259, 740, 743, 1013], 'J': [257, 260, 741, 744, 1014], 'Ford': [258, 261, 742, 745], 'Division': [262, 406, 746, 890], 'Endocrinology': [264, 408, 748, 892, 1063], 'Metabolism,': [266, 410, 750, 894, 1065], 'Medicine,': [269, 288, 347, 413, 753, 772, 831, 897, 1068, 1076], 'McMaster': [270, 414, 754, 898, 1069], 'Hamilton,': [272, 416, 756, 900, 1071], 'ON,': [273, 417, 757, 901, 1072], 'Nathalie': [282, 284, 766, 768, 1016], 'Bedard': [283, 285, 767, 769], 'University': [290, 298, 349, 357, 495, 774, 782, 833, 841, 979, 1078, 1086, 1103], 'the': [292, 296, 351, 355, 776, 780, 835, 839, 1080, 1084, 1136, 1198, 1206, 1244, 1269, 1344, 1370, 1402, 1414, 1420, 1434, 1443, 1449, 1473, 1495, 1506, 1589, 1626, 1664, 1669, 1677, 1689, 1703, 1710, 1790, 1801, 1848, 1864, 1894, 2012, 2089, 2128, 2151, 2167, 2184, 2199, 2247, 2254, 2307, 2320, 2328, 2355, 2434, 2510, 2565, 2585, 2595, 2607, 2670, 2716, 2723, 2763, 2772, 2787, 2809, 2889, 2901, 2906, 2918, 2924, 2942, 2960, 2967, 2988, 3020, 3025, 3036, 3057, 3113, 3183, 3186, 3229, 3236, 3248, 3323, 3335, 3368, 3399, 3407, 3421, 3469, 3488, 3513, 3531, 3586, 3637, 3651, 3669, 3688, 3732, 3763, 3773, 3781, 3792, 3803, 3821, 3847, 3887, 3932, 3965, 4029, 4033, 4125, 4187, 4200, 4238], 'Institute': [294, 353, 778, 837, 1082], 'Health': [299, 358, 783, 842, 1087], 'Arnim': [311, 313, 795, 797, 1018], 'Pause': [312, 314, 796, 798], 'Simon': [339, 342, 823, 826, 1020], 'S': [340, 343, 824, 827, 1021], 'Wing': [341, 344, 825, 828], 'Sergio': [370, 373, 854, 857, 1023], 'Di': [371, 374, 855, 858, 1024, 1769, 1872], 'Marco': [372, 375, 856, 859, 1770, 1873, 2455], 'Gregory': [400, 403, 884, 887, 1026], 'R': [401, 404, 885, 888, 1027], 'Steinberg': [402, 405, 886, 889], 'Russell': [426, 429, 910, 913, 1029], 'G': [427, 430, 911, 914, 1030], 'Jones': [428, 431, 912, 915], 'Imed-Eddine': [456, 460, 940, 944, 1033], 'Gallouzi': [457, 461, 941, 945, 1034], 'Corresponding': [458, 942], 'Author': [459, 943, 990], '[email': [462, 464, 946, 948, 1115, 1117], 'protected]': [463, 465, 947, 949, 1118], 'orcid.org/0000-0003-4758-4835': [466, 950], 'Life': [484, 968], 'Sciences': [485, 489, 969, 973, 1093, 1097], 'Division,': [486, 970, 1094], 'College': [487, 971, 1095], 'Engineering,': [491, 975, 1099], 'Hamad': [492, 976, 1100], 'Bin': [493, 977, 1101], 'Khalifa': [494, 978, 1102], '(HBKU),': [496, 980, 1104], 'Doha,': [497, 981, 1105], 'Qatar': [498, 982, 1106], 'Information': [991], 'Hall1,2,': [994], 'Griss2,3,': [996], 'Ma1,2,': [999], 'Sanchez1,2,': [1002], 'Sadek1,2,': [1004], 'Tremblay1,2,': [1008], 'Mubaid1,2,': [1010], 'Omer1,2,': [1012], 'Ford4,': [1015], 'Bedard5,': [1017], 'Pause1,2,': [1019], 'Wing5,': [1022], 'Marco1,2,': [1025], 'Steinberg4,': [1028], 'Jones2,3': [1031], '*,*,1,2,6': [1035], '1Department': [1036], '2Rosalind': [1044], '3Department': [1053], '4Division': [1061], '5Department': [1074], '6Life': [1092], '*Corresponding': [1107], 'author.': [1108], 'Tel:': [1109], '+1': [1110], '514': [1111], '398': [1112], '4537;': [1113], 'E-mails:': [1114], 'protected];': [1116], 'EMBO': [1119], 'Mol': [1120], 'Med': [1121], '(2018)10:e8307https://doi.org/10.15252/emmm.201708307': [1122], 'PDFDownload': [1123], 'PDF': [1124], 'article': [1126], 'text': [1127], 'main': [1129], 'figures.': [1130], 'Peer': [1131], 'ReviewDownload': [1132], 'a': [1133, 1183, 1221, 1254, 1297, 1309, 1340, 1502, 1513, 1520, 1546, 1914, 1971, 1976, 2039, 2416, 2421, 2484, 2525, 2603, 2677, 2952, 3007, 3207, 3214, 3255, 3282, 3290, 3443, 3665, 3695, 3715, 3720, 3864, 3894, 3948, 3974, 3980, 4050], 'summary': [1134], 'editorial': [1137, 1141], 'decision': [1138, 1142], 'including': [1140], 'letters,': [1143], 'reviewer': [1144], 'comments': [1145], 'responses': [1148], 'to': [1149, 1152, 1224, 1228, 1264, 1322, 1363, 1404, 1753, 1800, 1863, 1986, 2000, 2010, 2033, 2088, 2106, 2146, 2226, 2237, 2259, 2299, 2349, 2367, 2419, 2509, 2535, 2661, 2722, 2786, 2856, 2913, 2940, 2949, 3066, 3075, 3088, 3144, 3353, 3366, 3406, 3455, 3462, 3707, 3731, 3839, 3936, 3947, 3972, 4099, 4108, 4122, 4199, 4221, 4226, 4285], 'feedback.': [1150], 'ToolsAdd': [1151], 'favoritesDownload': [1153], 'CitationsTrack': [1154], 'CitationsPermissions': [1155], 'ShareFacebookTwitterLinked': [1156], 'InMendeleyWechatReddit': [1157], 'Figures': [1158], '&': [1159, 1609, 1823, 1869, 2022, 2057, 2206, 2242, 3786, 3991], 'Info': [1160], 'Abstract': [1161], 'Activation': [1162, 1994, 2380], 'has': [1165, 1176, 1900, 1955, 1997, 2007, 2029, 3131, 3198, 3590, 3879, 3921, 3997], 'been': [1166, 1901, 1956, 1998, 2008, 2031, 3132, 3199, 3591, 3998], 'associated': [1167, 1400, 1957, 3536, 3579, 3592, 3663, 3898], 'with': [1168, 1252, 1353, 1401, 1433, 1442, 1491, 1522, 1561, 1737, 1958, 2078, 2139, 2198, 2319, 2327, 2408, 2429, 2632, 2669, 3110, 3185, 3204, 3267, 3304, 3310, 3350, 3471, 3537, 3580, 3593, 3664, 3676, 3702, 3742, 3857, 3899, 3910, 3927, 4295, 4312, 4316], 'pro-atrophic': [1169], 'signaling': [1170, 1795, 2003, 2141, 2430, 3969, 4003, 4023, 4054, 4163, 4293], 'in': [1171, 1181, 1217, 1284, 1316, 1351, 1377, 1469, 1471, 1584, 1746, 1749, 1789, 1903, 1917, 2038, 2114, 2194, 2371, 2404, 2425, 2447, 2590, 2622, 2635, 2645, 2946, 3062, 3166, 3178, 3210, 3217, 3231, 3258, 3264, 3293, 3337, 3348, 3383, 3398, 3571, 3582, 3585, 3611, 3633, 3668, 3674, 3690, 3698, 3794, 3807, 3853, 3979, 4000, 4004, 4024, 4069, 4169, 4297, 4308, 4314], 'muscle.': [1172, 1897], 'However,': [1173, 2027, 3081, 3815], 'also': [1175, 1559, 1892, 2030, 2160, 2507, 2548, 2963, 3228, 3295], 'anti-inflammatory': [1177, 2036, 2061, 2152], 'effects,': [1178], 'suggesting': [1179, 1267, 1412, 1447, 2353], 'that': [1180, 1197, 1268, 1349, 1413, 1448, 1489, 1516, 1598, 1617, 1700, 1833, 1847, 1889, 1911, 1984, 2064, 2157, 2169, 2171, 2277, 2354, 2427, 2487, 2560, 2616, 2932, 2970, 3049, 3134, 3161, 3170, 3182, 3201, 3288, 3645, 3679, 3791, 3891, 3905, 3931, 4116], 'cachexia,': [1182, 2150], 'syndrome': [1184, 1515], 'inflammatory-driven': [1186], 'wasting,': [1188, 2352, 3359], 'activation': [1190, 1418, 1792, 2066, 2262, 2395, 2589, 2866, 2903, 3120, 3996, 4118], 'could': [1191, 1500, 2067, 2159, 2174, 2396, 3944], 'be': [1192, 1265, 1501, 1744, 2068, 2107, 2662, 2917, 3945, 3973], 'beneficial.': [1193], 'Here': [1194], 'we': [1195, 1828, 2165, 2182, 2275, 2401, 2463, 2593, 2910, 2930, 2974, 3018, 3168, 3234, 3629, 3771, 4027, 4304], 'show': [1196, 3694], 'AICAR': [1201, 1232, 1240, 1258, 1280, 1396, 1428, 1452, 2220, 2287, 2314, 2346, 2364, 2384, 2468, 2474, 2503, 2633, 2690, 2870, 2933, 2961, 2985, 3050, 3082, 3111, 3360, 3378, 3752, 3832, 4017, 4092, 4130, 4160, 4317], 'suppresses': [1202], 'IFNγ/TNFα-induced': [1203, 2289, 2695, 3358], 'atrophy,': [1204, 1304, 1368, 2400], 'while': [1205, 2278, 2617, 2657, 3816, 4111], 'mitochondrial': [1207, 1214, 1331, 1408, 1921, 3286, 3457, 3595, 3609, 3631, 3717, 3769, 3869, 3876, 3902, 3918, 3953], 'inhibitor': [1208, 1246, 1436, 2322, 3284, 3783], 'metformin': [1209, 1398, 2249, 2387, 2476, 2505, 2693, 2872, 2998, 3363, 3800, 3817, 3873, 3914, 3935, 4019, 4132, 4319], 'does': [1210, 2659], 'not.': [1211], 'IFNγ/TNFα': [1212, 2282, 2545, 2950, 3041, 3703, 3743, 3824, 4313], 'impair': [1213], 'oxidative': [1215, 3583, 3599, 3903], 'respiration': [1216, 3287, 3535, 3584, 3632, 3760, 3774, 3796, 3812, 3838, 3877, 3904, 3919], 'myotubes': [1218, 1388, 2196, 2406, 2947, 2965, 2993, 3064, 3265, 3385, 3635, 3700, 4171, 4310], 'promote': [1220], 'metabolic': [1222, 1235, 1335, 1948, 2303, 3141, 3176, 3208, 3381, 3515], 'shift': [1223, 3697, 3895], 'aerobic': [1225, 1918, 3706], 'glycolysis,': [1226, 3294], 'similarly': [1227], 'metformin.': [1229, 2470], 'In': [1230, 1735, 2245, 2291, 2342, 2996, 3127, 3601, 3750, 3871, 3912], 'contrast,': [1231, 2246, 2997, 3751, 3872, 3913], 'partially': [1233, 2300, 3754], 'restored': [1234, 3074, 3755], 'function.': [1236, 3954], 'effects': [1238, 1271, 1394, 1450, 2037, 2312, 2356, 3747, 4290], 'were': [1241, 1250, 1361, 1399, 1429, 1440, 1453, 2315, 2347, 2822, 3072, 3453, 3552, 3802, 4250, 4320], 'prevented': [1242, 2288, 2987], 'Compound': [1247, 1437, 2323], 'C': [1248, 1438, 2324], 'reproduced': [1251], 'A-769662,': [1253, 1446], 'specific': [1255, 2330], 'activator.': [1257], 'A-769662': [1260, 2333, 2344], 'co-treatment': [1261, 2318, 2631, 2873, 3109, 3741, 3753, 3833, 3909, 3926], 'was': [1262, 1462, 2103, 2297, 2365, 2681, 2815, 2938, 3227, 3364, 3460, 3528, 3545, 3662, 4097, 4243], 'found': [1263, 1362, 2009, 2276, 2298, 2348, 2931, 3606, 3644, 3790], 'synergistic,': [1266], 'anti-cachectic': [1270, 1425], 'these': [1273, 2358, 3098, 3191, 3374, 4289], 'drugs': [1274], 'are': [1275, 1660, 1695, 2360, 2415, 2794, 2844, 3033, 3245, 3476, 3574, 4272], 'mediated': [1276, 1454], 'through': [1277, 1330, 2004, 2217, 2361], 'activation.': [1279, 1457], 'spared': [1281], 'mass': [1283, 1467, 1554, 2370], 'mouse': [1285], 'models': [1286, 1905, 2374, 3613], 'cancer': [1288, 1477, 1603, 2115, 4005], 'LPS': [1290], 'induced': [1291, 2073, 2647, 2684, 3273, 3372, 3719], 'atrophy.': [1292, 1391, 2163, 2290], 'Together,': [1293, 3687], 'our': [1294, 3232, 3677], 'findings': [1295, 3678], 'suggest': [1296, 2156], 'dual': [1298], 'function': [1299, 1409, 2062, 2304, 3596], 'during': [1302, 1410, 1494, 1842, 2132, 2149, 2564, 2867, 2888, 3091, 3797, 3883, 3925, 3939], 'inflammation-driven': [1303, 1909], 'wherein': [1305], 'it': [1306, 1595, 1697, 1899, 2158, 2680, 3130, 3827, 3843], 'can': [1307, 1558, 1743, 2144], 'play': [1308], 'protective': [1310], 'role': [1311, 2129], 'when': [1312, 1327, 2679, 3012, 3308], 'activated': [1313, 1328, 2284, 2663], 'exogenously': [1314], 'early': [1315, 1496], 'disease': [1317, 1623, 1630], 'progression,': [1318], 'may': [1320, 3189], 'contribute': [1321, 2145], 'anabolic': [1323, 2002, 3968, 4002, 4022, 4162, 4292], 'suppression': [1324], 'atrophy': [1326, 1569, 1708, 1742, 2072, 2193, 2440, 2697, 2990, 3004, 3938, 3978], 'later': [1329], 'dysfunction': [1332, 3610], 'subsequent': [1334], 'stress.': [1336], 'Synopsis': [1337], 'Cachexia': [1338, 1511, 1541], 'is': [1339, 1512, 1542, 1596, 1614, 1676, 1698, 1709, 1839, 1970, 2123, 2221, 2488, 2524, 2532, 3163, 3863, 3906, 3961, 3970, 4080, 4106], 'co-morbidity': [1341], 'characterized': [1342, 1544, 3212], 'loss': [1345, 1468, 1550, 1562, 1679, 2448, 2943], 'skeletal': [1347, 1552, 1681, 2084], 'arises': [1350], 'patients': [1352, 1585, 1604], 'pro-inflammatory': [1354, 1524, 1714, 2200, 3984], 'diseases,': [1355, 1525], 'like': [1356], 'cancer.': [1357], 'Activators': [1358], 'protect': [1364, 3354], 'against': [1365, 3357], 'inflammation-induced': [1366], 'demonstrating': [1369], 'potential': [1371, 3956], 'targeting': [1373], 'therapy': [1376], 'cachexia.': [1378], 'activator': [1381, 1445, 2332], 'AICAR,': [1382, 1458, 2279, 2293, 3321, 3858, 3943], 'protected': [1386, 2964], 'C2C12': [1387, 2405, 3634, 3699], 'from': [1389, 2833, 2839, 2966, 3411, 3563, 3704, 4261, 4267], 'IFNγ/TNFα-driven': [1390], 'differential': [1393], 'ability': [1403, 3352], 'restore': [1405, 2301, 2368, 3085, 3836], 'or': [1406, 1775, 2871, 3355, 4143, 4318], 'inhibit': [1407, 2306], 'inflammation,': [1411], 'mechanism': [1415, 3976], 'affects': [1419], 'outcome': [1421], 'treatment.': [1423, 2613, 2687, 2713, 2736, 2755, 2894, 2982, 3435], 'properties': [1426], 'impaired': [1430, 3594, 3901], 'treatment': [1432, 1490, 1631, 2283, 2496, 2506, 2546, 2619, 2668, 2784, 2908, 2962, 2986, 3042, 3068, 3083, 3093, 3172, 3184, 3276, 3342, 3404, 3647, 3681, 3737, 3801, 3915, 4067], 'synergistic': [1441], 'effective': [1463, 2108], 'at': [1464, 2109, 2481, 2517, 2554, 2627, 2676, 4039, 4048], 'preventing': [1465, 2110], 'mice': [1470, 3203], 'both': [1472, 2473, 3104, 3650, 3756, 3808], 'C26': [1474], 'model': [1475, 1482, 2418], 'cachexia': [1478, 1499, 1583, 1606, 1620, 1867, 1907, 2116, 3205, 3615, 4006], 'an': [1480, 2099, 2124, 2232, 2260, 3472, 3705], 'endotoxin': [1481], 'sepsis.': [1484], 'Collectively,': [1485, 3886], 'study': [1487], 'suggests': [1488, 1888, 2063, 2142, 3930], 'activators': [1493], 'stages': [1497], 'novel': [1503], 'avenue': [1504], 'development': [1507], 'therapies.': [1509], 'Introduction': [1510], 'often': [1517, 2533], 'occurs': [1518], 'as': [1519, 1527, 1855, 2231, 3302, 3530, 3735], 'comorbidity': [1521], 'chronic': [1523, 1711, 2075], 'such': [1526, 1854], 'cancer,': [1528], 'HIV': [1529], 'infection,': [1530], 'sepsis': [1532], '(Fearon': [1533, 1572, 1684], 'et': [1534, 1538, 1573, 1577, 1639, 1643, 1647, 1651, 1655, 1685, 1722, 1726, 1732, 1762, 1766, 1771, 1778, 1782, 1807, 1811, 1815, 1819, 1874, 1879, 1883, 1924, 1928, 1932, 1936, 1940, 1944, 1965, 1991, 2018, 2045, 2049, 2053, 2095, 2118, 2210, 2271, 2335, 2339, 2456, 2498, 2574, 2578, 3148, 3152, 3156, 3194, 3220, 3318, 3617, 3621, 3625, 3987, 4011, 4057, 4061, 4089, 4151, 4155], 'al,': [1535, 1539, 1574, 1578, 1640, 1644, 1648, 1652, 1656, 1686, 1723, 1727, 1733, 1763, 1767, 1772, 1779, 1783, 1808, 1812, 1816, 1820, 1875, 1880, 1884, 1925, 1929, 1933, 1937, 1941, 1945, 1966, 1992, 2019, 2046, 2050, 2054, 2096, 2119, 2211, 2272, 2336, 2340, 2457, 2499, 2575, 2579, 3149, 3153, 3157, 3195, 3221, 3319, 3618, 3622, 3626, 3988, 4012, 4058, 4062, 4090, 4152, 4156], '2011;': [1536, 1813, 1817, 2047, 2051, 3619], 'Blum': [1537], '2014).': [1540, 1612, 1946], 'primarily': [1543], 'progressive': [1547], 'extensive': [1549], 'strength,': [1556], 'present': [1560], 'fat': [1564], 'mass,': [1565], 'anorexia,': [1566], 'cardiac': [1568], 'remodeling': [1571], '2012;': [1575, 1649, 1780, 1821, 1877, 1930, 1934, 2500, 3150, 3623], 'Groarke': [1576], '2013).': [1579, 1825, 1968, 2059, 2581, 3158, 3222, 3627, 4013], 'prevalence': [1581], 'varies': [1586], 'depending': [1587], 'on': [1588, 2923, 3002, 3322, 3330, 3430, 4139, 4145, 4291], 'type': [1590], 'disease.': [1592], 'For': [1593, 1826], 'example,': [1594, 1827], 'estimated': [1597], 'approximately': [1599], 'half': [1600], 'all': [1602], 'experience': [1605], '(von': [1607], 'Haehling': [1608], 'Anker,': [1610], '2010,': [1611], 'It': [1613, 3197, 4105], 'well': [1615], 'established': [1616, 2900], 'onset': [1618], 'negatively': [1621], 'impacts': [1622], 'outcome,': [1624], 'reducing': [1625], 'effectiveness': [1627], 'primary': [1629, 1704], 'increasing': [1633, 2266], 'patient': [1634], 'morbidity': [1635], 'mortality': [1637], '(Andreyev': [1638], '1998;': [1641], 'Prado': [1642], '2007;': [1645, 2020, 2024, 2208, 4059], 'Utech': [1646], 'Vaughan': [1650], '2013;': [1653, 1938, 1942, 2055, 3154], 'Vigano': [1654], '2017).': [1657], 'While': [1658, 2136], 'there': [1659, 2122, 3862], 'numerous': [1661], 'symptoms': [1662], 'state,': [1666], 'one': [1667, 1701], 'debilitating': [1671], 'aspects': [1672], 'condition': [1675], 'dramatic': [1678, 3666, 3696], 'tissue': [1683, 2112], '2011).': [1687, 1885, 3788], 'Although': [1688], 'mechanisms': [1690], 'behind': [1691], 'complex,': [1696], 'believed': [1699], 'triggers': [1705], 'elevation': [1712, 3726], 'cytokines': [1715, 2201, 2414, 3312, 3892], '(e.g.,': [1716], 'IL-1,': [1717], 'IL-6,': [1718], 'TNFα,': [1719], 'IFNγ)': [1720], '(Morley': [1721], '2006;': [1724, 2337, 4153], 'Argiles': [1725], '2009;': [1728, 1730, 1881], 'Tisdale,': [1729, 3992], 'Fearon': [1731, 1818], '2012).': [1734, 1993, 2212, 2273, 2459, 3196, 3320, 4157], 'keeping': [1736, 3349, 3675], 'this,': [1738], 'induction': [1739], 'recapitulated': [1745, 2326], 'culture': [1747], 'vivo': [1750], 'exposure': [1752, 1787, 1891, 3589], 'different': [1754, 2907], 'cytokine': [1755, 1786, 1890, 2612, 2618, 2665, 2686, 2868, 2981, 3067, 3092, 3171, 3341, 3646, 3680, 3736, 3798, 3884, 3940, 4066], 'combinations': [1756], '[e.g.,': [1757], 'IFNγ': [1758, 2202, 2409], 'TNFα': [1760, 2204], '(Guttridge': [1761, 1806], '2000;': [1764, 1809], 'Acharyya': [1765], '2004;': [1768], '2005,': [1773, 1876, 2458], '2012)': [1774], 'IL-6': [1776], '(Bonetto': [1777], 'White': [1781, 1931, 2577], '2012)].': [1784], 'Extended': [1785], 'results': [1788, 3099], 'continued': [1791], 'inflammatory': [1794, 3311], 'within': [1796, 2433, 2540, 3035], 'cells,': [1798, 3180], 'leading': [1799, 2258], 'expression': [1802, 2013, 3022], 'pro-cachectic': [1804, 2308, 2413], 'genes': [1805], 'Bonetto': [1810], 'Bonaldo': [1822], 'Sandri,': [1824], 'others': [1830], 'have': [1831, 2034, 3605, 4114], 'demonstrated': [1832, 3133, 4115], 'inducible': [1834], 'nitric': [1835, 1856], 'oxide': [1836, 1857], 'synthase': [1837], '(iNOS)': [1838], 'dramatically': [1840], 'upregulated': [1841], 'cytokine-driven': [1843, 2162, 2176], 'production': [1849, 3260, 3298, 3395], 'reactive': [1851], 'nitrogen': [1852], 'compounds,': [1853], '(NO),': [1858], 'enzyme': [1861], 'contributes': [1862], 'pathogenesis': [1865], '(Buck': [1868], 'Chojkier,': [1870], '1996;': [1871], 'Ramamoorthy': [1878], 'Recent': [1886], 'evidence': [1887, 3607], 'alters': [1893], 'metabolism': [1895, 3126, 3709, 3960], 'Indeed,': [1898, 3964], 'shown': [1902, 1999, 2032, 2105, 3200], 'several': [1904, 3603], 'undergoes': [1913], 'Warburg-like': [1915, 3215], 'increase': [1916, 2011, 3216, 3257, 3292, 3307, 3336, 3667], 'glycolysis': [1919, 3218, 3272, 3329, 3338, 3897], 'abnormalities': [1922], '(Barreiro': [1923], '2005;': [1926], 'Julienne': [1927, 3620], 'Der-Torossian': [1935, 3151], 'Fontes-Oliveira': [1939, 3155], 'McLean': [1943], 'regulating': [1949], 'enzyme,': [1950], 'AMP-activated': [1951], 'protein': [1952, 3464, 4035, 4045, 4167, 4209, 4299], 'kinase': [1953, 4037], '(AMPK),': [1954, 2882], 'cytokine-': [1959], 'cancer-driven': [1961], '(White': [1964, 4010], '2011,': [1967, 2580], 'heterotrimeric': [1972], 'complex': [1973], '(composed': [1974], 'catalytic': [1977], 'α-subunit,': [1978], 'linker': [1979], 'β-subunit,': [1980], 'regulatory': [1982], 'γ-subunit)': [1983], 'responds': [1985], 'cellular': [1987, 2224, 3380, 3514], 'energy': [1988], 'levels': [1989, 2269, 2553, 2637, 2774, 3023, 3059, 3078, 3090, 4229], '(Hardie': [1990, 2497, 3193], 'suppress': [2001], 'mTOR': [2005, 4009, 4055, 4123], 'muscle-specific': [2015], 'E3-ligases': [2016], '(Krawiec': [2017], 'Nakashima': [2021], 'Yakabe,': [2023], 'Shaw,': [2025], '2009).': [2026], 'potent': [2035], 'variety': [2040, 3981], 'cell': [2042], 'types': [2043], '(Galic': [2044], 'Salminen': [2048], 'Mounier': [2052], "O'Neill": [2056], 'Hardie,': [2058, 2207, 2243], 'beneficial': [2069], 'inflammation.': [2076], 'Consistent': [2077], 'concept,': [2080], 'genetic': [2081], 'deletion': [2082], 'leads': [2087, 4121], 'acceleration': [2090], 'aging-induced': [2092], 'sarcopenia': [2093], '(Bujak': [2094], '2015).': [2097], 'Further,': [2098, 3159], 'stabilizing': [2101], 'peptide': [2102], 'recently': [2104], 'adipose': [2111], '(Rohm': [2117], '2016).': [2120], 'Therefore,': [2121, 3347, 3628, 3852], 'apparent': [2125], 'contradiction': [2126], 'wasting:': [2135], 'its': [2137, 3331, 3840, 4042, 4146], 'association': [2138], 'atrophic': [2140], 'functions': [2153], 'prevent': [2161, 2175, 2351, 2397, 2941, 3367, 4100], 'Here,': [2164], 'tested': [2166, 2594], 'hypothesis': [2168], 'compounds': [2170, 2214, 2359, 3105], 'activate': [2172, 2215, 2461], 'wasting.': [2178, 2378, 2928, 3118], 'To': [2179, 2391, 2460, 2582, 2957, 3223, 3767, 4014, 4301], 'do': [2180, 4302], 'so,': [2181, 4303], 'assessed': [2183, 3019, 3630], 'impact': [2185], 'two': [2187, 2465], 'well-known': [2188], 'activators—AICAR': [2190], 'metformin—on': [2192], 'cultured': [2195], 'treated': [2197, 2407, 3266, 3701, 4311], '(Towler': [2205, 2241], 'Viollet': [2209, 3317], 'These': [2213, 2412], 'distinct': [2218], 'mechanisms.': [2219], 'phosphorylated': [2222], 'kinases': [2225], 'form': [2227], 'ZMP,': [2228], 'which': [2229, 3032, 3244, 4079, 4309], 'acts': [2230], 'AMP': [2233, 2268], 'mimetic,': [2234], 'binding': [2235], 'directly': [2236, 4286], 'activating': [2239, 3106], '2007).': [2244, 2341, 4063, 4091], 'biguanide': [2248], 'inhibits': [2250], 'Complex': [2251], 'I': [2252], 'electron': [2255], 'transport': [2256], 'chain,': [2257], 'indirect': [2261], 'cytoplasmic': [2267], '(Viollet': [2270], 'Surprisingly,': [2274, 2929], 'AMPK,': [2285, 2462, 2705, 3107], 'only': [2286, 2984, 3108], 'addition,': [2292, 2343, 3602], 'normal': [2302, 3124], 'iNOS/NO': [2309], 'pathway.': [2310], 'blocked': [2316], '(Cool': [2334], 'Goransson': [2338], 'synergistically': [2350], 'AMPK.': [2362], 'Finally,': [2363, 3017], 'able': [2366, 2939, 3365, 4098], 'multiple': [2372], 'murine': [2373], 'Results': [2379], 'assess': [2392, 3224, 3456, 3768, 4015], 'whether': [2393, 2959, 3225, 4288], 'cytokine-induced': [2398, 2989, 3003, 3116], 'performed': [2402, 3429, 3454, 4305], 'studies': [2403], 'TNFα.': [2411], 'well-established': [2417, 2526], 'induce': [2420, 3893], 'wasting-like': [2423], 'phenotype': [2424], 'vitro': [2426], 'begins': [2428], 'events': [2431], 'occurring': [2432], 'first': [2435, 2608, 2816, 2890, 3037, 3546, 4244], '24': [2436, 2493, 2555, 2609, 2781, 2891, 3038, 3401, 3432], 'h,': [2437, 2556, 2629], 'followed': [2438], 'detectable': [2441, 2623, 2636, 2648], '48': [2443, 2752, 2978, 4075], 'h': [2444, 2453, 2494, 2610, 2653, 2734, 2753, 2782, 2892, 2979, 3039, 3402, 3433, 4076], 'culminating': [2446], 'integrity': [2450, 2945], '72': [2452, 2733], '(Di': [2454], 'used': [2464, 2534, 3013, 4133], 'activators,': [2467], 'As': [2471, 3712, 4064], 'expected,': [2472, 3303, 3713, 4065], 'showed': [2477, 3006], 'increased': [2478, 2511, 2537, 2549, 2673, 3056, 3296, 3369], 'phosphorylation': [2480, 2512, 2562, 2596, 2624, 2650, 4030, 4140], 'Thr172': [2482], '(pAMPK),': [2483, 2703, 2879], 'post-translational': [2485], 'modification': [2486], 'required': [2489], 'activity,': [2492], 'after': [2495, 2712, 2735, 2754, 2783, 2980, 3403, 3434, 3468, 3778, 4077], 'Fig': [2501, 3659], '1A).': [2502, 2521], 'led': [2508], 'acetyl-CoA': [2514], 'carboxylase': [2515, 2523], '(ACC)': [2516], 'Ser79': [2518], '(pACC)': [2519], '(Fig': [2520, 2571, 2641, 2654, 2955, 2994, 3015, 3043, 3079, 3094, 3277, 3313, 3343, 3685, 3710, 3738, 3748, 3765, 3813, 3828, 3850, 4086, 4103, 4148], 'Acetyl-CoA': [2522], 'downstream': [2527, 4051], 'target': [2528, 4043, 4052], 'demonstrate': [2536, 3101], 'activity': [2539, 2675, 3177, 3573], 'cells': [2541, 3431, 3855], '(Munday,': [2542], '2002).': [2543], 'Interestingly,': [2544, 3830], 'alone': [2547, 2620, 3014, 3874, 3916], 'pAMPK': [2550], 'pACC': [2552], 'corroborating': [2557], 'previous': [2558, 4112], 'reports': [2559, 3604, 4113], 'increases': [2563, 3682], 'progression': [2566, 2925, 3114], 'cachexia-induced': [2568], '1A;': [2572], 'Penna': [2573], '2010;': [2576], 'further': [2583], 'understand': [2584], 'dynamics': [2586], 'model,': [2592, 3233], 'status': [2597, 2904, 4031], 'ACC': [2601, 2626, 2649, 2710, 2887], 'over': [2602, 2951], 'time': [2604, 2678], 'course': [2605, 2863], 'We': [2614, 3047, 3253, 3643, 3789, 4282], 'observed': [2615, 3048, 3254], 'resulted': [2621, 2634, 4068], '6–12': [2628], 'respectively,': [2630], '30': [2639], 'min': [2640], 'EV1).': [2642, 2655], 'Metformin': [2643, 3740], 'treatment,': [2644, 2666, 2934, 3051, 3941, 4078, 4093], 'turn,': [2646], '1': [2652], 'Thus,': [2656], 'seem': [2660], 'eventually,': [2667], 'agonists': [2672, 2922, 3188], 'normally': [2683], 'Figure': [2688, 2860, 3376, 4158], '1.': [2689], 'myotube': [2696, 2765, 2972, 2976, 3117, 3179], 'A.': [2698], 'Western': [2699, 2874, 4172], 'blotting': [2700, 2875, 4173], 'phospho-Thr172-AMPK': [2702], 'total': [2704, 2709, 2880, 2886, 4177, 4183], 'phospho-Ser79-ACC': [2706, 2883], '(pACC),': [2707, 2884], '24h': [2711], 'Quantification': [2714, 2761, 4185, 4213], 'represents': [2715, 2762, 4186, 4214], 'pAMPK/AMPK': [2717], 'pACC/ACC': [2719], 'ratios': [2720, 4197], 'relative': [2721, 2785, 3405, 3463, 4198, 4225], 'non-treated': [2724, 3076, 3408, 3841, 4201], '(NT)': [2725, 3409, 4202], 'control.': [2726, 2789, 4203], 'B.': [2727, 3387], 'Phase': [2728], 'contrast': [2729], 'images': [2730], 'fibers': [2732, 3146], 'Scale': [2737, 2756], 'bars': [2738, 2757, 2804, 3419, 3486, 4236], 'represent': [2739, 2758, 2805, 3420, 3487, 4237], '0.25': [2740], 'mm.': [2741], 'C.': [2742], 'Immunofluorescence': [2743], 'staining': [2744, 4223], 'myoglobin': [2746], 'myosin': [2748], 'heavy': [2749], 'chain': [2750], '(MyHC)': [2751], '50': [2759], 'μm.': [2760], 'average': [2764], 'width.': [2766], 'D,': [2767], 'E.': [2768], 'RT–qPCR': [2769], 'analysis': [2770, 3428, 3889, 4205], 'mRNA': [2773, 3021, 3058, 3087], 'MyoD': [2776, 3029, 3061], '(D)': [2777, 3500], 'myogenin': [2779], '(E)': [2780, 3505], 'NT': [2788, 2834, 3564, 4227, 4262], 'Data': [2790, 3475, 3540, 4233], 'information:': [2791, 3541, 4234], 'All': [2792], 'quantifications': [2793], 'three': [2796, 3412, 3479], 'independent': [2797, 3413, 3480], 'experiments': [2798, 3414, 4307], '(n': [2799, 3415, 3482, 4189, 4194, 4230], '=': [2800, 3416, 3483, 4190, 4195, 4231], '3)': [2801, 4191], 'error': [2803, 2807], 'standard': [2806, 3489], 'mean': [2810], '(SEM).': [2811], 'Significance': [2812, 2820, 3542, 3550, 4240, 4248], 'between': [2813, 3543, 4241], 'means': [2814, 3544, 4242], 'determined': [2817, 3547, 4028, 4245], 'using': [2818, 2824, 3548, 3554, 3636, 4211, 4246, 4252], 'ANOVA.': [2819, 3549, 4247], 'P-values': [2821, 3551, 4249], 'calculated': [2823, 3529, 3553, 4251], "Fisher's": [2825, 3555, 4253], 'LSD.': [2826, 3556, 4254], '*P': [2827, 3557, 4255], '<': [2828, 2831, 2837, 3558, 3561, 4256, 4259, 4265], '0.05;': [2829, 3559, 4257], '**P': [2830, 3560, 4258], '0.01': [2832, 2838, 3562, 4260, 4266], 'controls;': [2835, 4263], '††P': [2836, 4264], 'IFNγ/TNFα-treated': [2840, 4268], 'controls.': [2841, 3565, 4269], 'data': [2843, 4271], 'available': [2845, 4273], 'online': [2846, 4274], 'figure.': [2849, 2859, 4277], 'Download': [2850, 2852, 2895, 2897, 3566, 3568, 4278, 4280], 'figure': [2851, 2896, 3567, 4279], 'PowerPoint': [2853, 2898, 3569, 4281], 'Click': [2854], 'here': [2855, 4134], 'expand': [2857], 'EV1.': [2861], 'Time': [2862], 'phospho-Thr172': [2877], 'AMPKα': [2878, 2881], 'Having': [2899], 'across': [2905], 'regimes,': [2909], 'next': [2911, 4283], 'sought': [2912, 4284], 'determine': [2914, 2958, 4287], 'what': [2915], 'would': [2916, 3173], 'effect': [2919, 3001, 3882, 3924, 4138], 'exposed': [2948], '72-h': [2953], 'period': [2954], '1B).': [2956], 'initial': [2968], 'atrophying': [2969], 'precedes': [2971], 'collapse,': [2973], 'measured': [2975, 3235, 3397, 3467], 'widths': [2977, 3011], 'Again,': [2983], '1C).': [2995, 3016], 'had': [2999, 3744, 4135], 'no': [3000, 3305, 3745, 3880, 3922, 4136], 'trend': [3008], 'toward': [3009, 3896], 'smaller': [3010], 'pro-myogenic': [3026], 'transcription': [3027], 'factors': [3028], 'myogenin,': [3031], 'down-regulated': [3034], '1D': [3044], 'E).': [3046], 'significantly': [3055, 3174, 3648, 3825], 'cytokine-treated': [3063, 3384, 3854, 4025, 4170], 'compared': [3065, 3143, 3772], 'alone,': [3069], 'though': [3070, 3576, 3729], 'they': [3071], 'control': [3077, 3410, 4228], '1D).': [3080], 'did': [3084, 3326, 3818, 3834, 3844], 'Myogenin': [3086], 'basal': [3089, 3534, 3652, 3757, 3795, 3837], '1E).': [3095], 'Taken': [3096], 'together,': [3097], 'clearly': [3100], 'that,': [3102, 4110], 'despite': [3103], 'AICAR-mediated': [3119], 'restores': [3123, 4161], 'recent': [3128], 'years,': [3129], 'undergoing': [3136], 'exhibit': [3139, 3206], 'altered': [3140, 3959], 'profiles': [3142], 'healthy': [3145], '(Julienne': [3147], 'given': [3160], 'intimately': [3164], 'involved': [3165], 'metabolism,': [3167], 'predicted': [3169], 'alter': [3175], 'affect': [3190, 3328, 3820, 4021], 'changes': [3192, 3382, 3581, 4296], 'tumor-bearing': [3202], 'signature': [3209], '(Der-Torossian': [3219], 'case': [3230], 'rate': [3237, 3249, 3371, 3672], 'glucose': [3239, 3262, 3300, 3390], 'consumption': [3240, 3263, 3391, 3497, 3656], 'lactate': [3242, 3259, 3297, 3394], 'production,': [3243], 'indicative': [3246, 3269, 4081], 'glycolytic': [3251, 3370, 3572, 3683, 3708], 'flux.': [3252], 'significant': [3256, 4137], 'IFNγ/TNFα,': [3268], 'elevated': [3271], '2A': [3278, 3314, 3344], 'B).': [3280, 3346], 'Metformin,': [3281], 'known': [3283, 3716], 'induces': [3289], 'compensatory': [3291], 'consumption,': [3301], 'additional': [3306, 3746], 'co-treated': [3309, 3856], 'B;': [3316], 'other': [3324], 'hand,': [3325], 'own': [3332, 4147], 'reduced': [3334, 3598, 3649, 3762, 3826, 3962, 4083], 'caused': [3339], 'their': [3351], 'cytokines.': [3375, 3928], '2.': [3377], 'corrects': [3379], 'A,': [3386], 'Rates': [3388], '(A)': [3392], '(B)': [3396], 'media': [3400], '3).': [3417, 3484, 4232], 'Error': [3418, 3485, 4235], 'SEM.': [3422, 4239], 'C–F.': [3423], 'Seahorse': [3424, 3638], 'XF': [3425, 3639], 'extracellular': [3426, 3640, 3670], 'flux': [3427, 3641, 3684], 'Sequential': [3436], 'injections': [3437], 'oligomycin': [3439, 3784], '(Oligo.),': [3440], 'FCCP,': [3441], 'combination': [3444, 4315], 'rotenone': [3446], 'antimycin': [3448], 'A': [3449], '(Rot.': [3450], '+': [3451], 'AmA)': [3452], 'fitness.': [3458], 'Flux': [3459], 'normalized': [3461], 'units': [3465], '(RPU)': [3466], 'run': [3470], 'SRB': [3473], 'assay.': [3474], 'representative': [3477], 'experiment': [3481], 'deviation': [3490], 'biological': [3492], 'replicates': [3493], '(SD).': [3494], '(C)': [3495], 'Oxygen': [3496], 'rates': [3498, 3503, 3657, 3775], '(OCR).': [3499], 'Extracellular': [3501], 'acidification': [3502, 3671], '(ECAR).': [3504], 'Coordinate': [3506], 'plot': [3507], 'OCR': [3509, 3691, 3724], 'ECAR': [3511, 3693, 3764], 'showing': [3512], 'profile.': [3516], '(F)': [3517], 'Measurements': [3518], 'uncoupled': [3520, 3811], '(oligomycin-resistant)': [3521], 'coupled': [3523, 3538, 3809], '(oligomycin-sensitive)': [3524], 'respiration.': [3525, 3539, 3870], 'Coupling': [3526], 'efficiency': [3527, 3849], 'percentage': [3532], 'Changes': [3570], 'often,': [3575], 'always,': [3578], 'mitochondria.': [3587], 'Cytokine': [3588], 'capacity.': [3600], 'pre-clinical': [3612], '(Constantinou': [3616], 'Tzika': [3624], 'system.': [3642], 'maximal': [3654, 3759], 'oxygen': [3655], '(OCR;': [3658], '2C).': [3660], 'This': [3661, 3929], '(ECAR),': [3673], '2D).': [3686], 'shifts': [3689], '2E).': [3711], 'inhibitor,': [3718], 'similar': [3721], 'inhibition': [3722, 3966], 'ECAR,': [3728], 'same': [3733], 'magnitude': [3734], '2C–E).': [3739, 3749, 3766], 'coupling,': [3770], 'before': [3776], 'injection': [3779], 'ATP-synthase': [3782], '(Brand': [3785], 'Nicholls,': [3787], 'decreases': [3793], 'result': [3804], 'reductions': [3806], '2F).': [3814, 3829, 3851], 'coupling': [3822, 3848], 'efficiency,': [3823], 'although': [3831], 'levels,': [3842], 'fully': [3845], 'recover': [3846, 3937], 'recovery': [3865, 3881, 3951], 'ATP': [3867], 'synthesis-dependent': [3868], 'impairs': [3875, 3917], 'co-treatment.': [3885], 'metabolomics': [3888], 'shows': [3890], 'severely': [3900], 'blunted': [3907], 'AICAR.': [3911], 'additive': [3923], 'inability': [3933], 'unlike': [3942], 'due': [3946], 'lack': [3949], 'One': [3955], 'consequence': [3957], 'anabolism.': [3963], 'considered': [3971], 'key': [3975], 'underlying': [3977], 'overlying': [3983], 'conditions': [3985], '(Rennie': [3986], '1983;': [3989], 'Smith': [3990], '1993).': [3993], 'Furthermore,': [3994], 'implicated': [3999], 'suppressing': [4001], 'inhibiting': [4008], 'how': [4016], 'treatments': [4020], 'myotubes,': [4026], 'ribosomal': [4034, 4044], 'S6': [4036, 4046, 4074, 4144], '(S6K)': [4038], 'Thr389': [4040], '(S6)': [4047], 'Ser235/236,': [4049], '(Hornberger': [4056], 'Roux': [4060, 4088], 'hypo-phosphorylation': [4070], 'S6K': [4072, 4142], 'translation': [4084], 'initiation': [4085], '3A;': [4087, 4149], 'decrease': [4102], '3A).': [4104], 'important': [4107], 'note': [4109], 'exogenous': [4117], 'suppression,': [4124], 'dosage': [4126], 'timing': [4128], 'Williamson': [4150], 'Xu': [4154], '3.': [4159], 'de': [4165, 4207], 'novo': [4166, 4208], 'synthesis': [4168, 4210], 'phospho-Thr389-p70S6K': [4175], '(pS6K),': [4176], 'p70S6K': [4178], '(S6K),': [4179], 'phospho-Ser235/236-S6': [4180], '(pS6),': [4181], 'S6.': [4184], 'pS6K/S6K': [4188], 'pS6/S6': [4193], '4)': [4196], 'Radiographic': [4204], '35S-labeling.': [4212], 'whole': [4215], 'lane': [4216], 'radiation': [4217], 'signal': [4218], 'density': [4219], 'standardized': [4220], 'Coomassie': [4222], 'correlated': [4294], 'general': [4298], 'biosynthesis.': [4300], 'radio-labeling': [4306], 'i': [4321]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2806099235', 'counts_by_year': [{'year': 2024, 'cited_by_count': 6}, {'year': 2023, 'cited_by_count': 12}, {'year': 2022, 'cited_by_count': 9}, {'year': 2021, 'cited_by_count': 14}, {'year': 2020, 'cited_by_count': 10}, {'year': 2019, 'cited_by_count': 14}], 'updated_date': '2024-12-14T07:10:40.829206', 'created_date': '2018-06-13'}
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