| First Author | Stockebrand M | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 10 | Pages | 4147-56 |
| PubMed ID | 23825223 | Mgi Jnum | J:201173 |
| Mgi Id | MGI:5511111 | Doi | 10.1096/fj.12-225136 |
| Citation | Stockebrand M, et al. (2013) Differential regulation of AMPK activation in leptin- and creatine-deficient mice. FASEB J 27(10):4147-4156 |
| abstractText | AMP-activated protein kinase (AMPK) is a key sensor and regulator of energy homeostasis. Previously, we demonstrated that intracellular energy depletion by l-arginine:glycine amidinotransferase (AGAT) deficiency resulted in AMPK activation and protected from metabolic syndrome. In the present study, we show tissue-specific leptin dependence of AMPK activation by energy depletion. We investigated leptin-dependent AMPK regulation in AGAT- and leptin-deficient (d/d ob/ob) mice. Like ob/ob mice, but unlike d/d mice, d/d ob/ob mice were obese and glucose intolerant. Therefore, leptin is a prerequisite for resistance to metabolic syndrome in AGAT-deficient mice. Quantitative Western blots revealed a 4-fold increase in AMPK activation in skeletal muscle of d/d ob/ob mice (P<0.001). However, AMPK activation was absent in white adipose tissue (WAT) and liver. Compared with blood glucose levels in ob/ob mice, fasting levels were still reduced and therefore did not show leptin dependence (wild-type, 79.4+/-3.9 mg/dl; d/d, 68.4+/-3.2 mg/dl; P<0.05). In ob/ob mice and wild-type mice, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), in combination with leptin, augmented glucose tolerance compared with AICAR alone, whereas no improvement was found under conditions of high-fat-diet feeding. These findings reveal a previously unknown synergistic AMPK activation by leptin and intracellular energy depletion, suggesting that AMPK activation can be therapeutically effective in metabolic syndrome only if leptin sensitivity is preserved.-Stockebrand, M., Sauter, K., Neu, A., Isbrandt, D., Choe, C. Differential regulation of AMPK activation in leptin- and creatine-deficient mice. |
