Angiotensin AT1R expressing cells within the ventral hypothalamus modulate integrative control of cardiometabolic functions

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-05-30 DOI:10.1016/j.isci.2025.112797

Jhonatan Pasos , Valerie A. Wagner , Samuel B.R. Lawton , Alyssa M. Madison , Kush Nandani , Natalia M. Mathieu , Connie C. Grobe , John J. Reho , Bonnie P. Freudinger , Alexander J. Sherman , Daniel T. Brozoski , Lisa L. Morselli , Colin M.L. Burnett , Jeffrey L. Segar , Pablo Nakagawa , Curt D. Sigmund , Justin L. Grobe

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引用次数: 0

Abstract

Subtypes of agouti-related peptide (AgRP) neurons can be distinguished based upon expression of angiotensin II receptors. The type 1 subtype, which expresses the angiotensin type 1 receptor (Agtr1a), was examined for its role in the integrative control of cardiometabolic functions. Mice expressing Cre-recombinase via the Agtr1a locus received bilateral microinjection of an AAV vector encoding Cre-dependent expression of caspase-3 into the arcuate nucleus of mice housed at 22°C or 30°C. Ablation of Agtr1a⁺ cells caused increased food intake, adiposity, resting metabolic rate and shifts in nutrient partitioning, elevated temperature preference, loss of core temperature defense, and changes in blood pressure and heart rate. Many phenotypes were ameliorated by housing animals at thermoneutrality. Thus, Agtr1a⁺ cells in the ventral hypothalamus (including the type 1 AgRP neuron) influence cardiometabolic control through modulation of thermoregulatory responses to cold. Some functions of these cells appear to oppose canonical roles of other AgRP neuron subtypes.

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下丘脑腹侧表达血管紧张素AT1R的细胞调节心脏代谢功能的综合控制

针刺相关肽（AgRP）神经元的亚型可以根据血管紧张素II受体的表达来区分。1型亚型表达血管紧张素1型受体（Agtr1a），研究了其在心脏代谢功能综合控制中的作用。通过Agtr1a基因座表达cre -重组酶的小鼠，在22°C或30°C条件下，将编码cre依赖性caspase-3表达的AAV载体双侧微量注射到小鼠弓形核中。Agtr1a+细胞消融导致食物摄入增加、肥胖、静息代谢率和营养分配改变、温度偏好升高、核心温度防御丧失以及血压和心率变化。在热中性条件下饲养动物可以改善许多表型。因此，下丘脑腹侧Agtr1a+细胞（包括1型AgRP神经元）通过调节对寒冷的体温调节反应来影响心脏代谢控制。这些细胞的某些功能似乎与其他AgRP神经元亚型的典型作用相反。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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