title: Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice.
abstract: Gangliosides are widely involved in the regulation of cells and organs. However, little is known about their roles in adipose tissues and hypothalamus. In GD3 synthase-knockout (GD3S KO) mice, deletion of b-series gangliosides resulted in the reduction of serum leptin due to disturbed secretion from adipocytes. To examine whether leptin signals altered, leptin/leptin receptor (ObR)-mediated signaling in hypothalamus was analyzed. Hypothalamus of GD3S KO mouse showed increased expression of GM1 and GD1a, and increased activation of ObR-mediated signals such as pSTAT3 and c-Fos. Leptin stimulation of hypothalamus-derived N-41 cells and their transfectants with GD3S cDNA showed that a-series gangliosides positively regulate leptin/ObR-mediated signals. Co-precipitation analysis revealed that ObR interacts with a-series gangliosides with increased association by leptin stimulation. In brown adipose tissues (BAT) of GD3S KO mice, their weights and adipocyte numbers were increased, and BAT markers such as PGC1α and UCP-1 were also up-regulated. These results suggested that leptin/ObRb-mediated signals were enhanced in hypothalamus of GD3S KO mice due to increased a-series gangliosides, leading to the apparently similar features of energy expenditure between the KO and wild type mice.
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Shuting
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Tokizane
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan; Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan; Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Yuhsuke
authors.initials: Y
authors.lastname: Ohmi
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Banno
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okajima
authors.affiliation: Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyama
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan; Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan; Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai 487-8501, Japan. Electronic address: keikofu@isc.chubu.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D017667:Adipocytes / Q000166:cytology; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics; D012799:Sialyltransferases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005732:Gangliosides; D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C021298:ganglioside, GD1a; D005677:G(M1) Ganglioside; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
keywords: Ganglioside; Hypothalamus; Leptin; Receptor; STAT3