Abstract MP47: Cardiac Compensation And Altered CREB/ERK Signaling Within The Arcuate Nucleus In The C57BL/6J Mouse Model Of Selective Leptin Resistance
العنوان: | Abstract MP47: Cardiac Compensation And Altered CREB/ERK Signaling Within The Arcuate Nucleus In The C57BL/6J Mouse Model Of Selective Leptin Resistance |
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المؤلفون: | Curt D. Sigmund, Jing Wu, Kirthikaa Balapattabi, Vanessa Oliveira, Justin L. Grobe, Tina Wan, John J Reho, Caitlin C. O'Meara |
المصدر: | Hypertension. 76 |
بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | medicine.medical_specialty, Leptin, digestive, oral, and skin physiology, Erk signaling, Biology, medicine.disease, CREB, Obesity, Endocrinology, Arcuate nucleus, Internal medicine, C57bl 6j mouse, Internal Medicine, medicine, biology.protein, Leptin resistance, Signal transduction |
الوصف: | Prolonged obesity causes “selective leptin resistance” (SLR), in which cardiovascular responses to leptin are intact but metabolic responses are lost. High fat diet (HFD) for 10 weeks causes SLR in C57BL/6J mice, as it attenuates metabolic (adipose) sympathetic nervous activity (SNA) responses to leptin but has no effect on cardiovascular SNA responses. Using single-nucleus RNAsequencing, we recently discovered disruption of leptin and CREB signaling specifically in Agouti-related peptide ( Agrp ) neurons of the arcuate nucleus of the hypothalamus (ARC) after 10-week HFD. Because C57BL/6J mice are generally resistant to diet-induced changes in blood pressure (BP), one goal of this study was to examine BP in this model. Further, we sought to examine effects of prolonged HFD on CREB signaling and Agrp mRNA within the ARC. Male C57BL/6J mice were maintained on chow (2920x) or HFD (D12451) from 8-18 weeks of age. Intake behaviors were studied in metabolic cages and bomb calorimetry; body composition via nuclear magnetic resonance; BP and HR via radiotelemetry; and cardiac function via echocardiography. ARC biopsies were analyzed for Agrp mRNA via qPCR and for CREB and ERK proteins using capillary electrophoresis-based Western. HFD increased caloric uptake, leading to increases in body and fat mass (pAgrp mRNA in the ARC. We conclude that prolonged HFD increases cardiovascular SNA in C57BL/6J mice without effect on BP because of cardiac compensation. Further, this model causes SLR at the level of the ARC Agrp neuron, in a mechanism likely involving alterations in CREB- and ERK-mediated signaling. |
تدمد: | 1524-4563 0194-911X |
DOI: | 10.1161/hyp.76.suppl_1.mp47 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::cdba440666de08c3f4231b18139c04f6 https://doi.org/10.1161/hyp.76.suppl_1.mp47 |
رقم الانضمام: | edsair.doi...........cdba440666de08c3f4231b18139c04f6 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15244563 0194911X |
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DOI: | 10.1161/hyp.76.suppl_1.mp47 |