Central leptin and resistin combined elicit enhanced central effects on renal sympathetic nerve activity

Abstract

New Findings r What is the central question of this study?Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether a combination of resistin and leptin could induce a greater response than either alone. We also used Fos protein to quantify the number of activated neurons in the brain. r What is the main finding and its importance?A combination of leptin and resistin induced a greater increase in RSNA than either hormone alone. This was correlated with a greater number of activated neurons in the arcuate nucleus than with either hormone alone.Leptin and resistin act centrally to increase renal sympathetic nerve activity (RSNA). We investigated whether a combination of resistin and leptin could induce a greater response than either alone. Mean arterial pressure, heart rate and RSNA were recorded before and for 3 h after intracerebroventricular saline (control; n = 5), leptin (7 µg; n = 5), resistin (7 µg; n = 4) and leptin administered 15 min after resistin (n = 6). Leptin alone and resistin alone significantly increased RSNA (74 ± 17 and 50 ± 14%, respectively; P < 0.0001 compared with saline). When leptin and resistin were combined, there was a significantly greater increase in RSNA (163 ± 23%) compared with either hormone alone (P < 0.0001). Maximal responses of mean arterial pressure and heart rate were not significantly different between groups. We also used Fos protein to quantify the number of activated neurons in the brain. Compared with controls, there were significant increases in numbers of Fos-positive neurons in the arcuate and hypothalamic paraventricular nuclei when leptin or resistin was administered alone or when they were combined, and in the lamina terminalis when leptin and resistin were combined. Only in the arcuate nucleus was the increase significantly greater compared with either hormone alone. The findings show that a combination of leptin and resistin induces a greater RSNA increase and a greater number of activated neurons in the arcuate nucleus than with either hormone alone. Given that leptin makes an important contribution to the elevated RSNA observed in obese and overweight conditions, the increased concentrations of leptin and resistin may mean that the contribution of leptin to the elevated RSNA in those conditions is enhanced.

The metabolic syndrome and chronic kidney disease

“…[70] Although the mechanisms of resistin-related kidney injury is less clear, studies have shown that it upregulates expression of Intercellular Adhesion Molecule-1 and vascular cell adhesion molecule-1. [71] In addition, both leptin and resistin enhance renal sympathetic nerve activity,[72] the latter possibly via phosphatidylinositol 3-kinase. [73]…”

Effects of central administration of resistin on renal sympathetic nerve activity in rats fed a high‐fat diet: a comparison with leptin

“…RSNA was amplified using a low‐noise differential amplifier (models ENG 187B and 133; Baker Institute, Melbourne, VIC, Australia), filtered (band pass 100‐1000 Hz), rectified and integrated at 0.5 second intervals. The signals were recorded using a PowerLab data acquisition system (ADInstruments) . The background electrical noise levels were determined post mortem and subtracted from the nerve activity obtained in the anaesthetised rat.…”

“…The MAP, HR and RSNA were measured before and for 180 minutes after administration of saline vehicle (n=5; 5 μL), leptin (7 μg in 5 μL; n=4), resistin (7 μg in 5 μL; n=5) and the combination of both resistin and leptin (n=6; leptin was administered 15 minutes after resistin). The doses of each hormone were chosen on the basis of previous studies . At the end of the experiment, the epididymal fat was removed and weighed.…”

“…The changes in RSNA, MAP and HR over time following leptin alone, resistin alone and the combination of leptin and resistin were compared between high=fat and normal chow diets using two‐way ANOVA. Data for the normal chow fed rats used for this comparison have been reported previously . The calculated maximum responses were compared between the dietary groups using Student's unpaired t test.…”

“…Because resistin, similar to leptin, increases renal sympathetic nerve activity, we investigated whether a high‐fat diet could influence the sympatho‐excitatory effects induced by resistin. Furthermore, we also explored whether a high‐fat diet would influence the increase in RSNA induced by the combination of resistin and leptin because the combined effect of resistin and leptin in normal chow fed rats results in significantly greater sympatho‐excitatory actions on RSNA …”