Central resistin enhances renal sympathetic nerve activity via phosphatidylinositol 3-kinase but reduces the activity to brown adipose tissue via extracellular signal-regulated kinase 1/2.
Resistin is an adipokine, originally identified in adipose tissue, and its plasma levels are elevated in obesity. Characteristics of obesity include impaired metabolic regulation and cardiovascular dysfunction, such as increased sympathetic nerve activity (SNA) to the kidney and skeletal muscle vasculature. Resistin can affect energy homeostasis through central mechanisms that include reduced food intake and reduced thermogenesis, and can also increase lumbar SNA via a central action. The present study investigated: (i) the effect of centrally-administered resistin on SNA targeting the kidney and (ii) the intracellular signalling pathways mediating the changes in SNA innervating the kidney and brown adipose tissue (BAT) induced by resistin. Intracerebroventricular resistin (7 μg) injected into overnight fasted, anaesthetised rats induced a significant increase in renal SNA by approximately 40%. This response was prevented when phosphatidylinositol 3-kinase (PI3K) was inhibited by i.c.v. administration of LY294002 (5 μg). Resistin reduced BAT SNA and this response was delayed by 150 min when extracellular-regulated kinase (ERK)1/2 was inhibited by i.c.v. administration of U0126. The findings indicate that resistin increases renal SNA via PI3K and reduces BAT SNA via ERK1/2.
School of Medical Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Victoria, Australia.
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Kosari
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JA
Rathner
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Badoer
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D052243:Resistin; D058539:Phosphatidylinositol 3-Kinase; D048052:Mitogen-Activated Protein Kinase 3