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RESISTIN ENHANCES THE CENTRAL EFFECTS OF LEPTIN ON RENAL SYMPATHETIC NERVE ACTIVITY
Author(s) -
Habeeballah Hamza,
Alsuhaymi Naif,
Stebbing Martin,
Jenkins Trisha,
Badoer Emilio
Publication year - 2016
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.30.1_supplement.765.1
Subject(s) - resistin , leptin , medicine , endocrinology , hormone , adipose tissue , adipokine , obesity
Background Leptin is a well known hormone released from fat tissue and acts centrally to influence metabolic and cardiovascular functions. It increases renal sympathetic nerve activity (RSNA) and could be an important contributor to the abnormally elevated RSNA observed in obesity or overweight conditions. Resistin is also a hormone released from fat tissue and acts centrally to elicit effects on RSNA similar to those of leptin. The question arises as to whether resistin can enhance leptin's actions on RSNA. Although the brain nuclei activated by leptin are well known, there has not been a systematic investigation of those activated by resistin. We investigated the effects of acute central administration of leptin and resistin on RSNA. We also used Fos protein to quantify the number of activated neurons in the brain following each treatment. Aim To measure RSNA in response to leptin and resistin alone and in combination, and determine the effect on the distribution of Fos in autonomic brain nuclei Methods RSNA, mean arterial pressure (MAP) and heart rate (HR) in anaesthetised Sprague‐Dawley male rats were recorded before and for 3 hours after intracerebroventricular saline (control, n=5), leptin (7 μg; n=5), resistin (7 μg; n=4) and the combination of both resistin and leptin (administered 15 minutes after resistin,n=6). At the end of the experiment the animals were perfused with 4% paraformaldehyde and immunohistochemistry was performed on brain sections. Results Leptin alone and resistin alone significantly increased RSNA (74±17%, 50±14% respectively) (P<0.0001 from saline). When resistin and leptin were combined there was a significantly greater increase in RSNA (163±23%; P<0.0001, compared to either drug alone). Changes in MAP and HR from pre‐drug levels were not significantly different between groups. The distribution of Fos‐positive cell nuclei elicited by resistin was similar to leptin. When leptin and resistin were combined, the increase in the number of Fos‐positive neurons in the arcuate nucleus, and in the lamina terminalis, was significantly greater than control. Conclusion The findings show that leptin and resistin, combined, enhance RSNA as well as Fos production in the arcuate nucleus and lamina terminalis. Since leptin makes an important contribution to the elevated RSNA observed in obese / overweight conditions, the increased leptin and resistin levels may mean the contribution of leptin to the elevated RSNA in those conditions is enhanced.