 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, April 1, 2001, 21(7):2413-2424
Leptin-Induced Nuclear Translocation of STAT3 Immunoreactivity in Hypothalamic Nuclei Involved in Body Weight Regulation
Thomas Hübschle1, Elke Thom1, Anna Watson1, Joachim Roth2, Susanne Klaus1, and Wolfgang Meyerhof1 1 German Institute of Human Nutrition, Departments of Biochemistry and Physiology of Nutrition and Molecular Genetics, D-14558 Potsdam-Rehbrücke, Germany, and 2 Institute of Veterinary Physiology, Justus-Liebig-University, D-35392 Giessen, Germany
Leptin is involved in the hypothalamic control of food intake and body weight. Fos immunohistochemistry has been used to functionally map leptin target neurons involved in these regulatory processes. However, only a subset of hypothalamic neurons expressing the long form of the leptin receptor (Ob-Rb) also coexpress the neuronal activation marker Fos after leptin stimulation. To functionally map all leptin target neurons, regardless of whether leptin-mediated neuronal activation or inhibition occurs, we immunohistochemically investigated the leptin-induced nuclear translocation of the signal transducer and activator of transcription molecule STAT3, which represents a crucial step in the regulation of leptin-dependent gene expression. As proven by colocalization studies with the nuclear 4',6-diamidino-2-phenylindole dilactate stain, intracerebroventricular leptin treatment, but not intracerebroventricular application of pyrogen-free saline, induced a time-dependent nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei, with strong nuclear STAT3 signals detectable in the arcuate nucleus, the lateral hypothalamus, and the ventromedial and dorsomedial hypothalamic nuclei. This leptin-induced STAT3 translocation pattern proved to be distinct from that induced by interleukin-6, another cytokine using STAT3 in its signaling pathway. Combined immunohistochemical STAT3 and Fos detection after leptin treatment revealed a higher number of STAT3-positive than Fos-positive cell nuclei in the aforementioned hypothalamic structures and showed that Fos immunoreactivity colocalized only in a subset of all leptin-responsive STAT3 nuclei. These results suggest that the detection of nuclear STAT3 immunoreactivity represents a new neuroanatomical tool to functionally map central leptin actions. They further support the importance of ventrally located caudal hypothalamic structures representing the main leptin targets involved in body weight regulation.
Key words: hypothalamus; food intake; appetite control; leptin; interleukin-6; cytokines; transcription factors; signal transducers and activator of transcription; STAT3; c-Fos; immunohistochemistry; confocal microscopy
Copyright © 2001 Society for Neuroscience 0270-6474/01/2172413-12$05.00/0
This article has been cited by other articles:
B. G. Irani, C. Le Foll, A. Dunn-Meynell, and B. E. Levin
Effects of Leptin on Rat Ventromedial Hypothalamic Neurons
Endocrinology, October 1, 2008; 149(10): 5146 - 5154.
[Abstract] [Full Text] [PDF]
N. C. Bingham, K. K. Anderson, A. L. Reuter, N. R. Stallings, and K. L. Parker
Selective Loss of Leptin Receptors in the Ventromedial Hypothalamic Nucleus Results in Increased Adiposity and a Metabolic Syndrome
Endocrinology, May 1, 2008; 149(5): 2138 - 2148.
[Abstract] [Full Text] [PDF]
A.-S. Carlo, M. Pyrski, C. Loudes, A. Faivre-Baumann, J. Epelbaum, L. M. Williams, and W. Meyerhof
Leptin Sensitivity in the Developing Rat Hypothalamus
Endocrinology, December 1, 2007; 148(12): 6073 - 6082.
[Abstract] [Full Text] [PDF]
J. Ferezou-Viala, A.-F. Roy, C. Serougne, D. Gripois, M. Parquet, V. Bailleux, A. Gertler, B. Delplanque, J. Djiane, M. Riottot, et al.
Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1056 - R1062.
[Abstract] [Full Text] [PDF]
L. Shen, P. Tso, S. C. Woods, R. R. Sakai, W. S. Davidson, and M. Liu
Hypothalamic Apolipoprotein A-IV Is Regulated by Leptin
Endocrinology, June 1, 2007; 148(6): 2681 - 2689.
[Abstract] [Full Text] [PDF]
L. Huo, L. Maeng, C. Bjorbaek, and H. J. Grill
Leptin and the Control of Food Intake: Neurons in the Nucleus of the Solitary Tract Are Activated by Both Gastric Distension and Leptin
Endocrinology, May 1, 2007; 148(5): 2189 - 2197.
[Abstract] [Full Text] [PDF]
C. B. Kaelin, L. Gong, A. W. Xu, F. Yao, K. Hockman, G. J. Morton, M. W. Schwartz, G. S. Barsh, and R. G. MacKenzie
Signal Transducer and Activator of Transcription (Stat) Binding Sites But Not Stat3 Are Required for Fasting-Induced Transcription of Agouti-Related Protein Messenger Ribonucleic Acid
Mol. Endocrinol., October 1, 2006; 20(10): 2591 - 2602.
[Abstract] [Full Text] [PDF]
P. Pacher, S. Batkai, and G. Kunos
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462.
[Abstract] [Full Text] [PDF]
M. Perello, R. C. Stuart, and E. A. Nillni
The Role of Intracerebroventricular Administration of Leptin in the Stimulation of Prothyrotropin Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus
Endocrinology, July 1, 2006; 147(7): 3296 - 3306.
[Abstract] [Full Text] [PDF]
M. V. Kokoeva, H. Yin, and J. S. Flier
Neurogenesis in the Hypothalamus of Adult Mice: Potential Role in Energy Balance
Science, October 28, 2005; 310(5748): 679 - 683.
[Abstract] [Full Text] [PDF]
S. R. Ladyman and D. R. Grattan
Suppression of Leptin Receptor Messenger Ribonucleic Acid and Leptin Responsiveness in the Ventromedial Nucleus of the Hypothalamus during Pregnancy in the Rat
Endocrinology, September 1, 2005; 146(9): 3868 - 3874.
[Abstract] [Full Text] [PDF]
C. Sachot, S. Poole, and G. N Luheshi
Circulating leptin mediates lipopolysaccharide-induced anorexia and fever in rats
J. Physiol., November 15, 2004; 561(1): 263 - 272.
[Abstract] [Full Text] [PDF]
H. Munzberg, J. S. Flier, and C. Bjorbaek
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Endocrinology, November 1, 2004; 145(11): 4880 - 4889.
[Abstract] [Full Text] [PDF]
V. C. Russo, S. Metaxas, K. Kobayashi, M. Harris, and G. A. Werther
Antiapoptotic Effects of Leptin in Human Neuroblastoma Cells
Endocrinology, September 1, 2004; 145(9): 4103 - 4112.
[Abstract] [Full Text] [PDF]
C. Perrin, C. Knauf, and R. Burcelin
Intracerebroventricular Infusion of Glucose, Insulin, and the Adenosine Monophosphate-Activated Kinase Activator, 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside, Controls Muscle Glycogen Synthesis
Endocrinology, September 1, 2004; 145(9): 4025 - 4033.
[Abstract] [Full Text] [PDF]
S. R. Ladyman and D. R. Grattan
Region-Specific Reduction in Leptin-Induced Phosphorylation of Signal Transducer and Activator of Transcription-3 (STAT3) in the Rat Hypothalamus Is Associated with Leptin Resistance during Pregnancy
Endocrinology, August 1, 2004; 145(8): 3704 - 3711.
[Abstract] [Full Text] [PDF]
A. Sahu
Minireview: A Hypothalamic Role in Energy Balance with Special Emphasis on Leptin
Endocrinology, June 1, 2004; 145(6): 2613 - 2620.
[Abstract] [Full Text] [PDF]
S. G. Bouret and R. B. Simerly
Minireview: Leptin and Development of Hypothalamic Feeding Circuits
Endocrinology, June 1, 2004; 145(6): 2621 - 2626.
[Abstract] [Full Text] [PDF]
C. Rummel, T. Hubschle, R. Gerstberger, and J. Roth
Nuclear translocation of the transcription factor STAT3 in the guinea pig brain during systemic or localized inflammation
J. Physiol., June 1, 2004; 557(2): 671 - 687.
[Abstract] [Full Text] [PDF]
F. Guo, K. Bakal, Y. Minokoshi, and A. N. Hollenberg
Leptin Signaling Targets the Thyrotropin-Releasing Hormone Gene Promoter in Vivo
Endocrinology, May 1, 2004; 145(5): 2221 - 2227.
[Abstract] [Full Text] [PDF]
C. Bjorbaek and B. B. Kahn
Leptin Signaling in the Central Nervous System and the Periphery
Recent Prog. Horm. Res., January 1, 2004; 59(1): 305 - 331.
[Abstract] [Full Text]
B. E. Levin, A. A. Dunn-Meynell, and W. A. Banks
Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2004; 286(1): R143 - R150.
[Abstract] [Full Text]
J. M. Zigman and J. K. Elmquist
Minireview: From Anorexia to Obesity--The Yin and Yang of Body Weight Control
Endocrinology, September 1, 2003; 144(9): 3749 - 3756.
[Abstract] [Full Text] [PDF]
R. Pal and A. Sahu
Leptin Signaling in the Hypothalamus during Chronic Central Leptin Infusion
Endocrinology, September 1, 2003; 144(9): 3789 - 3798.
[Abstract] [Full Text] [PDF]
H. Munzberg, L. Huo, E. A. Nillni, A. N. Hollenberg, and C. Bjorbaek
Role of Signal Transducer and Activator of Transcription 3 in Regulation of Hypothalamic Proopiomelanocortin Gene Expression by Leptin
Endocrinology, May 1, 2003; 144(5): 2121 - 2131.
[Abstract] [Full Text] [PDF]
I. Swart, J. W. Jahng, J. M. Overton, and T. A. Houpt
Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2002; 283(5): R1020 - R1026.
[Abstract] [Full Text] [PDF]
T. Hosoi, T. Kawagishi, Y. Okuma, J. Tanaka, and Y. Nomura
Brain Stem Is a Direct Target for Leptin's Action in the Central Nervous System
Endocrinology, September 1, 2002; 143(9): 3498 - 3504.
[Abstract] [Full Text] [PDF]
E.-M. Harre, J. Roth, U. Pehl, M. Kueth, R. Gerstberger, and T. Hubschle
Molecular Biology of Thermoregulation: Selected Contribution: Role of IL-6 in LPS-induced nuclear STAT3 translocation in sensory circumventricular organs during fever in rats
J Appl Physiol, June 1, 2002; 92(6): 2657 - 2666.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|