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Adipose afferent reflex response to insulin is mediated by melanocortin 4 type receptors in the paraventricular nucleus in insulin resistance rats.
Acta Physiol (Oxf). 2015 Aug; 214(4):450-66.AP

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.

CONCLUSION

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+Show Affiliations

Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.Department of Neurology of Heze Minicipal Hospital, Heze, 274000, China.Clinical Laboratory of Luyi People's Hospital, Zhoukou, 466000, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.Department of Pediatrics, The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.Department of Pediatrics, The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.Department of Pediatrics, The Fourth Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25846948

Citation

Ding, L, et al. "Adipose Afferent Reflex Response to Insulin Is Mediated By Melanocortin 4 Type Receptors in the Paraventricular Nucleus in Insulin Resistance Rats." Acta Physiologica (Oxford, England), vol. 214, no. 4, 2015, pp. 450-66.
Ding L, Tong N, Feng XM, et al. Adipose afferent reflex response to insulin is mediated by melanocortin 4 type receptors in the paraventricular nucleus in insulin resistance rats. Acta Physiol (Oxf). 2015;214(4):450-66.
Ding, L., Tong, N., Feng, X. M., Chen, D., Wang, H. S., Wang, Y., Li, Y., Zhu, G. Q., & Zhou, Y. B. (2015). Adipose afferent reflex response to insulin is mediated by melanocortin 4 type receptors in the paraventricular nucleus in insulin resistance rats. Acta Physiologica (Oxford, England), 214(4), 450-66. https://doi.org/10.1111/apha.12502
Ding L, et al. Adipose Afferent Reflex Response to Insulin Is Mediated By Melanocortin 4 Type Receptors in the Paraventricular Nucleus in Insulin Resistance Rats. Acta Physiol (Oxf). 2015;214(4):450-66. PubMed PMID: 25846948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adipose afferent reflex response to insulin is mediated by melanocortin 4 type receptors in the paraventricular nucleus in insulin resistance rats. AU - Ding,L, AU - Tong,N, AU - Feng,X-M, AU - Chen,D, AU - Wang,H-S, AU - Wang,Y, AU - Li,Y, AU - Zhu,G-Q, AU - Zhou,Y-B, Y1 - 2015/04/20/ PY - 2014/10/29/received PY - 2014/11/27/revised PY - 2015/03/31/revised PY - 2015/04/01/accepted PY - 2015/4/8/entrez PY - 2015/4/8/pubmed PY - 2016/5/12/medline KW - adipose afferent reflex KW - insulin KW - insulin resistance KW - melanocortin 4 type receptors KW - paraventricular nucleus SP - 450 EP - 66 JF - Acta physiologica (Oxford, England) JO - Acta Physiol (Oxf) VL - 214 IS - 4 N2 - 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. CONCLUSION: 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. SN - 1748-1716 UR - https://www.unboundmedicine.com/medline/citation/25846948/Adipose_afferent_reflex_response_to_insulin_is_mediated_by_melanocortin_4_type_receptors_in_the_paraventricular_nucleus_in_insulin_resistance_rats_ L2 - https://doi.org/10.1111/apha.12502 DB - PRIME DP - Unbound Medicine ER -