title: Adipose afferent reflex response to insulin is mediated by melanocortin 4 type receptors in the paraventricular nucleus in insulin resistance rats.
abstract: BACKGROUND
  Adipose afferent reflex (AAR) contributes to sympathetic activation and hypertension. Paraventricular nucleus (PVN) plays an important role in AAR and sympathetic outflow. The aim of the present study was to determine whether PVN mediates AAR response to insulin in a rat model of insulin resistance (IR).
  
  
  METHODS
  Male Sprague-Dawley rats were randomly divided into Control and IR groups. Insulin resistance was induced by supplementing fructose (125 g L(-1) , 12 weeks) in the drinking water. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to injection of capsaicin into four sites of right inguinal white adipose tissue.
  
  
  RESULTS
  Rats in IR group showed a rise in plasma noradrenaline (NE), glucose, insulin and triglyceride levels, left ventricular weight, systolic blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR) and PVN glucose and insulin levels, melanocortin 4 type receptors (MC4Rs) protein expression, but not MC3Rs and insulin receptors. Compared with Control group, AAR in IR group was significantly enhanced, which contributed to the elevation of NE level; and insulin microinjection into the PVN or the third ventricle significantly strengthened AAR, which was attenuated by pre-treatment with MC4Rs antagonist HS024 and anti-insulin affibody, respectively, but not insulin receptors antagonist S961.
  
  
  CONCLUSIONS
  The enhanced AAR participates in sympathetic activation in IR, which can be strengthened by PVN insulin. PVN MC4Rs mediate the AAR response to insulin in IR, but not MC3Rs and insulin receptors.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Neurology of Heze Minicipal Hospital, Heze, 274000, China.
authors.forename: N
authors.initials: N
authors.lastname: Tong
authors.affiliation: Clinical Laboratory of Luyi People's Hospital, Zhoukou, 466000, China.
authors.forename: X-M
authors.initials: XM
authors.lastname: Feng
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: H-S
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Y-B
authors.initials: YB
authors.lastname: Zhou
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism* / Q000502:physiology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D007328:Insulin; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D012018:Reflex / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D007328:Insulin; D044105:Receptor, Melanocortin, Type 4
keywords: adipose afferent reflex; insulin; insulin resistance; melanocortin 4 type receptors; paraventricular nucleus