INVESTIGADORES
RUBINSTEIN Marcelo
artículos
Título:
Signal Transducer and Activator of Transcription-3 Is Required in Hypothalamic Agouti-Related Protein/Neuropeptide Y Neurons for Normal Energy Homeostasis
Autor/es:
LIJIE GONG; FAYI YAO; KRISTIN HOCKMAN; HENRY H. HENG; GREGORY J. MORTON; KIYOSHI TAKEDA; SHIZUO AKIRA; MALCOLM J. LOW; MARCELO RUBINSTEIN; ROBERT G. MACKENZIE
Revista:
ENDOCRINOLOGY
Editorial:
ENDOCRINE SOC
Referencias:
Año: 2008 vol. 149 p. 3346 - 3354
ISSN:
0013-7227
Resumen:
Signal transducer and activator of transcription (Stat)-3 signals
mediate many of the metabolic effects of the fat cellderived
hormone, leptin. In mice, brain-specific depletion of
either the long form of the leptin receptor (Lepr) or Stat3
results in comparable obese phenotypes as does replacement
of Lepr with an altered leptin receptor locus that codes for a
Lepr unable to interact with Stat3. Among the multiple brain
regions containing leptin-sensitive Stat3 sites, cells expressing
feeding-related neuropeptides in the arcuate nucleus of
the hypothalamus have received much of the focus. To determine
the contribution to energy homeostasis of Stat3 expressed
in agouti-related protein (Agrp)/neuropeptide Y
(Npy) arcuate neurons, Stat3 was deleted specifically from
these cells, and several metabolic indices were measured. It
was found that deletion of Stat3 from Agrp/Npy neurons resulted
in modest weight gain that was accounted for by increased
adiposity. Agrp/Stat3-deficient mice also showed hyperleptinemia,
and high-fat diet-induced hyperinsulinemia.
Stat3 deletion in Agrp/Npy neurons also resulted in altered
hypothalamic gene expression indicated by increased Npy
mRNA and decreased induction of suppressor of cytokine signaling-
3 in response to leptin. Agrp mRNA levels in the fed or
fasted state were unaffected. Behaviorally, mice without Stat3
in Agrp/Npy neurons were mildly hyperphagic and hyporesponsive
to leptin. We conclude that Stat3 in Agrp/Npy neurons
is required for normal energy homeostasis, but Stat3
signaling in other brain areas also contributes to the regulation
of energy homeostasis. (Endocrinology 149: 33463354,
2008)
2008)
Endocrinology 149: 33463354,
2008)