Leptin-induced basal Akt phosphorylation and its implication in exercise-mediated improvement of insulin sensitivity
- Foreign Trade and Business College, Chongqing Normal University, Chongqing (China)
- School of Physical Education, Hebei Normal University, Shijiazhuang (China)
Highlights: • Acute exercise stimulates leptin release while chronic exercise decreased basal serum leptin. • Leptin increased basal levels of insulin signaling and glucose uptake. • Leptin decreased insulin-stimulated insulin signaling and glucose uptake. • Blocking JAK2 signaling decreased leptin-stimulated insulin signaling. • Blocking JAK2 signaling restored leptin-attenuated insulin sensitivity. Physical exercise is an efficient therapeutical tool in the management of insulin resistance (IR) and related metabolic diseases. Leptin, the well-known obesity hormone and the absence of which leads to IR, showed controversial effects on IR as research continues. Thus, in this study, a detailed investigation of the effect of leptin on exercise-mediated improvement of insulin sensitivity and its underlying mechanism was carried out. Using a rat model of chronic or acute swimming exercise training, we found that serum leptin increased 1 h after either acute exercise or the last session of chronic exercise, when impaired insulin action was observed in previous reports. However, chronic exercise reducd basal serum leptin levels and promoted insulin sensitivity compared with sedentary controls or rats subjected to one bout of aerobic exercise. Our animal results indicated the potential linkage between leptin and insulin sensitivity, which is further investigated in the skeletal muscle L6 cells. Leptin treatment in L6 cells promoted the basal levels of insulin signaling as well as glucose uptake, while blocking JAK2 signaling with either pharmacological intervention (JAK2 inhibitor AG490) or genetic manipulation (siRNA knockdown) decreased the basal levels of insulin signaling. Furthermore, leptin treatment inhibited insulin-stimulated insulin signaling and glucose uptake, while blocking JAK2 signaling restored leptin-attenuated insulin sensitivity. Taken together, our results demonstrated that reduced serum leptin, at least in part, contributes to exercise-mediated improvement of insulin sensitivity, indicating JAK2 as a potent therapeutical target of insulin resistance.
- OSTI ID:
- 23127430
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 496, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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