title: Central leptin and resistin combined elicit enhanced central effects on renal sympathetic nerve activity.
abstract: 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. 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.
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
authors.forename: Hamza
authors.initials: H
authors.lastname: Habeeballah
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
authors.forename: Naif
authors.initials: N
authors.lastname: Alsuhaymi
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stebbing
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
authors.forename: Trisha A
authors.initials: TA
authors.lastname: Jenkins
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
authors.forename: Emilio
authors.initials: E
authors.lastname: Badoer
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D020738:Leptin; D052243:Resistin; D012965:Sodium Chloride