Premium
Soluble leptin receptor neutralizes leptin signaling and anorexic responses
Author(s) -
Zhang Jiejin,
Scarpace Philip J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.658
Subject(s) - leptin , leptin receptor , medicine , endocrinology , in vivo , receptor , chemistry , endogeny , biology , obesity , microbiology and biotechnology
Soluble leptin receptor (SLR) is the major leptin binding protein in the circulation. The SLR, presumably by reducing available free leptin, inhibits leptin signaling, in vitro and leptin transport across the blood‐brain barrier, in vivo . We hypothesized that central delivery of SLR will inhibit hypothalamic leptin signaling and leptin‐induced anorexic responses. Acute central co‐administration of SLR (13.5ug) and leptin (90ng) fully blocked the 3‐fold increase in hypothalamic STAT3 phosphorylation induced by leptin alone in F344XBN rats. When leptin (0.1mg/day) was infused peripherally for 7 days with a simultaneous central infusion of SLR (4.3ug/day), serum leptin levels were elevated to 14ng/ml, and were unaffected by simultaneous SLR infusion. Leptin induced a significant reduction in food intake (day 2–7 cumulative Δ= −27.4±2.7g) and body weight (Δmax = −14.3±0.8g). These responses were partially blocked by central SLR infusion (day 2–7 cumulative Δ = −17.5±3.3g, p <0.05, weight Δmax = −10±1.2g, p <0.01). In a separate experiment, 5.5ug/ul SLR was infused centrally and compared with ACSF infused control rats. The SLR infusion alone increased food intake and body weight, presumably by neutralizing endogenous leptin. Our results indicate that SLR partially neutralizes leptin signaling and anorexic responses, in vivo , and suggests greater doses of SLR will be able to completely inhibit leptin‐induced anorexic responses. Supported by NIH grant AG‐26159.