TY - JOUR
T1 - Mediobasal Hypothalamic p70 S6 Kinase 1 Modulates the Control of Energy Homeostasis
AU - Blouet, Clémence
AU - Ono, Hiraku
AU - Schwartz, Gary J.
N1 - Funding Information:
We thank Xiaosong Li for technical assistance. This work was supported by NIH DK 066618, New York Obesity Research Center DK026687, the Skirball Institute for Nutrient Sensing, and the French Society for the Study of Nutrition. G.J.S. and C.B. conceived the experiment; C.B. and H.O. carried it out; C.B. designed and carried out the data analysis; C.B. and G.J.S. cowrote the paper.
PY - 2008/12/6
Y1 - 2008/12/6
N2 - p70 S6 kinase 1 (S6K) is a major downstream effector of the mammalian target of rapamycin (mTOR), primarily implicated in the control of protein synthesis, cell growth, and proliferation. Here we demonstrate that specific bidirectional molecular targeting of mediobasal hypothalamic (MBH) S6K activity in rats is sufficient to significantly alter food intake, body weight, hypothalamic orexigenic neuropeptide expression, hypothalamic leptin sensitivity, and the metabolic and feeding responses to a fast. In addition, adenoviral-mediated constitutive activation of MBH S6K improved cold tolerance and protected against high-fat diet-induced overeating, fat deposition, and insulin resistance. Our results provide direct evidence that MBH S6K activity bidirectionally drives behavioral and metabolic determinants of energy balance and promote the assessment of MBH S6K activity as a therapeutic target in metabolic diseases.
AB - p70 S6 kinase 1 (S6K) is a major downstream effector of the mammalian target of rapamycin (mTOR), primarily implicated in the control of protein synthesis, cell growth, and proliferation. Here we demonstrate that specific bidirectional molecular targeting of mediobasal hypothalamic (MBH) S6K activity in rats is sufficient to significantly alter food intake, body weight, hypothalamic orexigenic neuropeptide expression, hypothalamic leptin sensitivity, and the metabolic and feeding responses to a fast. In addition, adenoviral-mediated constitutive activation of MBH S6K improved cold tolerance and protected against high-fat diet-induced overeating, fat deposition, and insulin resistance. Our results provide direct evidence that MBH S6K activity bidirectionally drives behavioral and metabolic determinants of energy balance and promote the assessment of MBH S6K activity as a therapeutic target in metabolic diseases.
KW - HUMDISEASE
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U2 - 10.1016/j.cmet.2008.10.004
DO - 10.1016/j.cmet.2008.10.004
M3 - Article
C2 - 19041762
AN - SCOPUS:56449115916
SN - 1550-4131
VL - 8
SP - 459
EP - 467
JO - Cell metabolism
JF - Cell metabolism
IS - 6
ER -