title: Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.
abstract: Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain.
authors: Neurobiochemistry Group, Unit of Biochemistry and Molecular Biology, Facultad de Medicina, Universidad de Alcalá, E-28871 Alcalá de Henares, Spain.
authors: A
authors: A
authors: Perianes-Cachero
authors: E
authors: E
authors: Burgos-Ramos
authors: L
authors: L
authors: Puebla-Jiménez
authors: S
authors: S
authors: Canelles
authors: L M
authors: LM
authors: Frago
authors: A
authors: A
authors: Hervás-Aguilar
authors: S
authors: S
authors: de Frutos
authors: M V
authors: MV
authors: Toledo-Lobo
authors: V
authors: V
authors: Mela
authors: M P
authors: MP
authors: Viveros
authors: J
authors: J
authors: Argente
authors: J A
authors: JA
authors: Chowen
authors: E
authors: E
authors: Arilla-Ferreiro
authors: V
authors: V
authors: Barrios
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007118:Immunoassay; D007276:Injections, Intraventricular; D007328:Insulin / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D017481:Receptors, Somatostatin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D007328:Insulin; D020738:Leptin; D017481:Receptors, Somatostatin; C115977:Sstr2 protein, rat; D013004:Somatostatin
keywords: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; AC; BSA; CRE; CRE binding protein; CREB; EDTA; ELISA; FK; HEPES; IRS1; JAK2; JNK; Janus kinase 2; MBIA; NDS; Ob-Rb; PMSF; SDS; SOCS3; SRIF; SRIF receptor subtype; STAT3; TBS; TTBS; Tris-buffered saline; Tris–Tween-buffered saline; adenylyl cyclase; bovine serum albumin; c-Jun N-terminal kinase; cyclic AMP response element; enzyme-linked immunosorbent assay; ethylenediaminetetraacetic acid; forskolin; frontoparietal cortex; hippocampus; icv; insulin receptor substrate 1; insulin signaling; intracerebroventricular; leptin; long-form of leptin receptor; multiplexed bead immunoassay; normal donkey serum; p; phenylmethylsulfonyl fluoride; phosphorylated; signal transducer and activator of transcription 3; sodium dodecyl sulfate; somatostatin; somatostatin receptors; sst; suppressor of cytokine signaling 3