title: Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus.
abstract: Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug-target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus-derived cell lines, termed adult mouse hypothalamus (AMH) cells, by developing transgenic mice in which SV40 Tag was overexpressed in chromogranin A-positive cells in a tamoxifen-dependent manner. In order to obtain leptin-responsive clones, we selected clones based on the phosphorylation levels of STAT3 induced by leptin. The selected clones were fairly responsive to leptin in terms of STAT3, ERK, and Akt phosphorylation and induction of c-Fos mRNA induction. Pretreatment with leptin, insulin, and palmitate attenuated the c-Fos mRNA response to leptin, suggesting that certain aspects of leptin resistance might be reconstituted in this cellular model. These cell lines are useful tools for understanding the molecular nature of the signal disturbance in the leptin-resistant state and for identifying potential target molecules for drugs that relieve leptin resistance, although they have drawbacks including de-differentiated nature and lack of long-time stability.
authors: Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Hiroshi
authors: H
authors: Iwakura
authors: Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Katsuko
authors: K
authors: Dote
authors: Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Mika
authors: M
authors: Bando
authors: Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Hiroyuki
authors: H
authors: Koyama
authors: Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Kiminori
authors: K
authors: Hosoda
authors: Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.|National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors: Kenji
authors: K
authors: Kangawa
authors: Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Kazuwa
authors: K
authors: Nakao
mesh_terms: D000818:Animals; D002460:Cell Line; D004351:Drug Resistance / Q000187:drug effects* / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D007328:Insulin; D020738:Leptin; D016761:Oncogene Proteins v-fos; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D013629:Tamoxifen; D048049:Extracellular Signal-Regulated MAP Kinases