title: Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
abstract: BACKGROUND
  The view that γ-aminobutyric acid (GABA) plays a functional role in non-neuronal tissues, in addition to an inhibitory neurotransmitter role in the mammalian central nervous system, is prevailing, while little attention has been paid to GABAergic signaling machineries expressed by adipocytes to date. In this study, we attempted to demonstrate the possible functional expression of GABAergic signaling machineries by adipocytes.
  
  
  RESULTS
  GABA(B) receptor 1 (GABA(B)R1) subunit was constitutively expressed by mouse embryonic fibroblasts differentiated into adipocytes and adipocytic 3T3-L1 cells in culture, as well as mouse white adipose tissue, with no responsiveness to GABA(B)R ligands. However, no prominent expression was seen with mRNA for GABA(B)R2 subunit required for heteromeric orchestration of the functional GABA(B)R by any adipocytic cells and tissues. Leptin mRNA expression was significantly and selectively decreased in adipose tissue and embryonic fibroblasts, along with drastically reduced plasma leptin levels, in GABA(B)R1-null mice than in wild-type mice. Knockdown by siRNA of GABA(B)R1 subunit led to significant decreases in leptin promoter activity and leptin mRNA levels in 3T3-L1 cells.
  
  
  CONCLUSIONS
  Our results indicate that GABA(B)R1 subunit is constitutively expressed by adipocytes to primarily regulate leptin expression at the transcriptional level through a mechanism not relevant to the function as a partner of heterodimeric assembly to the functional GABA(B)R.
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hinoi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takarada
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takahata
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujita
authors.forename: Saya
authors.initials: S
authors.lastname: Takada
authors.forename: Syota
authors.initials: S
authors.lastname: Hashizume
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating / Q000235:genetics / Q000502:physiology; D005260:Female; D015151:Immunoblotting; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D034622:RNA Interference; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D018080:Receptors, GABA-B