Role of the hypothalamic-pituitary-thyroid axis in metabolic regulation by JNK1.
The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mass is mediated, in part, by increased energy expenditure that is associated with activation of the hypothalamic-pituitary-thyroid axis. Disruption of thyroid hormone function prevents the effects of nervous system JNK1 deficiency on body mass. These data demonstrate that the hypothalamic-pituitary-thyroid axis represents an important target of metabolic signaling by JNK1.
Sabio
Guadalupe
G
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Cavanagh-Kyros
Julie
J
Barrett
Tamera
T
Jung
Dae Young
DY
Ko
Hwi Jin
HJ
Ong
Helena
H
Morel
Caroline
C
Mora
Alfonso
A
Reilly
Judith
J
Kim
Jason K
JK
Davis
Roger J
RJ
D000818:Animals; D004435:Eating; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism*; D015398:Signal Transduction; D013961:Thyroid Gland / Q000378:metabolism*
D007328:Insulin; D048055:Mitogen-Activated Protein Kinase 8