Leptin receptor expressing neurons express phosphodiesterase-3B (PDE3B) and leptin induces STAT3 activation in PDE3B neurons in the mouse hypothalamus |
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| Affiliation: | 1. Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;2. Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;1. Department of Psychiatry, University of Montreal, Quebec, Canada;2. Department of Neuroscience, University of Montreal, Quebec, Canada;1. Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA;2. Department of Pathology and Laboratory Medicine, University of California, Davis 4400 V Street, Sacramento, CA 95817, USA;3. Department of Psychiatry, University of California, Davis, 2805 50th St., Sacramento, CA 95817, USA;4. MIND Institute, University of California, Davis, 2825 50th Street, Sacramento, CA 95817, USA;5. Department of Pediatrics, University of California, Davis, 2825 50th Street, Sacramento, CA 95817, USA;6. Department of Biochemistry and Molecular Medicine, University of California, Davis, One Shields Avenue, CA 95616, USA;1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA;2. Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA;3. Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA;4. Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA;5. Department of Pathology & Microbiology, College of Medicine, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA;6. Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA;7. Department of Pathology and Tumor Biology, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan;1. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan;2. Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan;3. Okayama University Hospital, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan |
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| Abstract: | Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. Cumulative evidence suggests that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways including the phosphodiesterase-3B (PDE3B) pathway mediate leptin signaling in the hypothalamus. We have shown that PDE3B is localized in various hypothalamic sites implicated in the regulation of energy homeostasis and that the anorectic and body weight reducing effects of leptin are mediated by the activation of PDE3B. It is still unknown if PDE3B is expressed in the long form of the leptin-receptor (ObRb)-expressing neurons in the hypothalamus and whether leptin induces STAT3 activation in PDE3B-expressing neurons. In this study, we examined co-localization of PDE3B with ObRb neurons in various hypothalamic nuclei in ObRb-GFP mice that were treated with leptin (5 mg/kg, ip) for 2 h. Results showed that most of the ObRb neurons in the arcuate nucleus (ARC, 93%), ventromedial nucleus (VMN, 94%), dorsomedial nucleus (DMN, 95%), ventral premammillary nucleus (PMv, 97%) and lateral hypothalamus (LH, 97%) co-expressed PDE3B. We next examined co-localization of p-STAT3 and PDE3B in the hypothalamus in C57BL6 mice that were treated with leptin (5 mg/kg, ip) for 1 h. The results showed that almost all p-STAT3 positive neurons in different hypothalamic nuclei including ARC, VMN, DMN, LH and PMv areas expressed PDE3B. These results suggest the possibility for a direct role for the PDE3B pathway in mediating leptin action in the hypothalamus. |
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| Keywords: | Phosphodiesterase-3B ObRb p-STAT3 Hypothalamus Leptin |
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