| First Author | Benzler J | Year | 2012 |
| Journal | Biochem J | Volume | 447 |
| Issue | 1 | Pages | 175-84 |
| PubMed ID | 22849606 | Mgi Jnum | J:191319 |
| Mgi Id | MGI:5461442 | Doi | 10.1042/BJ20120834 |
| Citation | Benzler J, et al. (2012) Hypothalamic glycogen synthase kinase 3beta has a central role in the regulation of food intake and glucose metabolism. Biochem J 447(1):175-84 |
| abstractText | GSK3beta (glycogen synthase kinase 3beta) is a ubiquitous kinase that plays a key role in multiple intracellular signalling pathways, and increased GSK3beta activity is implicated in disorders ranging from cancer to Alzheimer's disease. In the present study, we provide the first evidence of increased hypothalamic signalling via GSK3beta in leptin-deficient Lep(ob/ob) mice and show that intracerebroventricular injection of a GSK3beta inhibitor acutely improves glucose tolerance in these mice. The beneficial effect of the GSK3beta inhibitor was dependent on hypothalamic signalling via PI3K (phosphoinositide 3-kinase), a key intracellular mediator of both leptin and insulin action. Conversely, neuron-specific overexpression of GSK3beta in the mediobasal hypothalamus exacerbated the hyperphagia, obesity and impairment of glucose tolerance induced by a high-fat diet, while having little effect in controls fed standard chow. These results demonstrate that increased hypothalamic GSK3beta signalling contributes to deleterious effects of leptin deficiency and exacerbates high-fat diet-induced weight gain and glucose intolerance. |
