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Mutation of Tyr985 of the leptin receptor differentially alters regional sympathetic activation to leptin
Author(s) -
Harlan Shan Marie,
Morgan Donald,
Dellsperger David,
Myers Martin,
Mark Allyn,
Rahmouni Kamal
Publication year - 2010
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.24.1_supplement.809.22
Subject(s) - leptin , medicine , endocrinology , leptin receptor , adipose tissue , brown adipose tissue , sympathetic nervous system , adipocyte , receptor , biology , chemistry , obesity , blood pressure
Leptin is an adipocyte derived hormone which acts in the brain to regulate food intake and energy expenditure. Leptin action in the brain also increases sympathetic nerve activity (SNA) to several beds including brown adipose tissue (BAT) and kidney. There is mounting evidence that the distinct signaling pathways downstream of the leptin receptor (LRb) may mediate selective leptin actions. We assessed the regional SNA response to leptin in mice ( l/l ) that carry a point mutation in LRb at Tyr985, which is involved in ERK activation by leptin. Multifiber recording of SNA was performed under α‐chloralose anesthesia in mice equipped with intracerebralventricular (ICV) cannula. As expected in wild type mice, ICV injection of leptin (2 μg) significantly (P<0.05 vs. vehicle) increased SNA subserving BAT and kidney. In contrast, l/l mice had a significantly (P=0.005) attenuated BAT SNA response to leptin (100±38%) as compared to wild type mice (456±130%). Renal SNA responses to leptin did not differ in l/l mice (154±80%) as compared to wild type controls (143±39%; P=NS). These data demonstrate the pivotal role of leptin receptor signaling emanating from the Tyr985 in the control of thermogenic sympathetic outflow. Our data also suggest that signaling from Tyr985 of the leptin receptor is not involved in leptin‐induced renal sympathetic activation. Together, these data demonstrate selectivity in leptin action. This work was funded by a Cardiovascular Interdisciplinary Research Fellowship, HL007121 to Shannon Harlan.