The role of agomelatine in appetite regulation and body weight in rats.

IF 2.8 4区医学 Q2 PHYSIOLOGY

Experimental Physiology Pub Date : 2025-08-13 DOI:10.1113/EP092783

Engin Korkmaz, Yavuz Erden, Çiğdem Tekin, Suat Tekin

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Abstract

The hypothalamic nuclei play a central role in the synthesis of anorexigenic and orexigenic neuropeptides, which are regulated by peripheral hormones, like leptin and ghrelin. Melatonergic receptors (MT₁/MT₂) are prominently expressed in the arcuate nucleus of the hypothalamus - an essential hub for appetite control - and in peripheral metabolic tissues where leptin and ghrelin are secreted. Agomelatine, an antidepressant drug and potent MT₁/MT₂ agonist, offers potential for modulating appetite. This study aimed to investigate the impact of agomelatine on appetite regulation. Forty male Sprague-Dawley rats were randomly allocated into four groups, control (no treatment), vehicle control, agomelatine 20 mg/kg (Ago-20), and agomelatine 40 mg/kg (Ago-40), and administered oral gavage for 14 days. Body weight and food intake were recorded daily. At the end of the experiment, rats were euthanized and blood and hypothalamic tissue samples were obtained. Agomelatine significantly reduced body weight (Ago-40: 275.2 ± 7.2 g vs. control: 339.7 ± 8.3 g, P < 0.05) and food intake (Ago-40: 20.21 ± 1.32 g vs. control: 32.09 ± 1.58 g, P < 0.05) by day 14, without affecting water intake. Plasma ghrelin levels decreased (Ago-40: 22.54 ± 3.95 ng/dL vs. control: 46.67 ± 4.84 ng/dL, P < 0.05), while leptin increased (Ago-40: 552.30 ± 41.67 pg/mL vs. control: 271.10 ± 32.12 pg/mL P < 0.05). Hypothalamic orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related peptide (AgRP) were suppressed (NPY, Ago40: 0.61 ± 0.02 vs. Control: 1.36 ± 0.1321; AgRP, Ago40: 0.52 ± 0.03 vs. Control: 1.49 ± 0.27, P < 0.05), while anorexigenic cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) were elevated (CART: Ago40: 1.19 ± 0.08 vs. Control: 0.92 ± 0.06; POMC: Ago40: 1.49 ± 0.17 vs. Control: 0.67 ± 0.10, P < 0.05). These findings suggest agomelatine promotes weight loss by modulating appetite-related hormones and hypothalamic neuropeptides, highlighting its potential as a therapeutic for obesity and metabolic disorders.

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阿戈美拉汀对大鼠食欲调节和体重的作用。

下丘脑核在厌氧神经肽和厌氧神经肽的合成中起着核心作用，这些神经肽受瘦素和胃饥饿素等外周激素的调节。褪黑激素受体（MT1/MT2）在下丘脑弓状核（控制食欲的重要中枢）和分泌瘦素和胃饥饿素的外周代谢组织中显著表达。阿戈美拉汀是一种抗抑郁药物和有效的MT1/MT2激动剂，具有调节食欲的潜力。本研究旨在探讨阿戈美拉汀对食欲调节的影响。选取雄性Sprague-Dawley大鼠40只，随机分为对照组（未处理）、载药对照组、阿戈美拉汀20 mg/kg （Ago-20）、阿戈美拉汀40 mg/kg (Ago-40) 4组，灌胃14 d。每天记录体重和食物摄入量。实验结束时，对大鼠实施安乐死，取血液和下丘脑组织标本。阿戈美拉汀显著降低第14天体重（Ago-40: 275.2±7.2 g，对照组：339.7±8.3 g, P < 0.05）和摄食量（Ago-40: 20.21±1.32 g，对照组：32.09±1.58 g, P < 0.05），但不影响摄水量。血浆ghrelin水平降低（Ago-40: 22.54±3.95 ng/dL，对照组：46.67±4.84 ng/dL, P < 0.05），而瘦素水平升高（Ago-40: 552.30±41.67 pg/mL，对照组：271.10±32.12 pg/mL, P < 0.05）。下丘脑产氧神经肽神经肽Y （NPY）和针刺相关肽（AgRP）均受到抑制(NPY、Ago40: 0.61±0.02 vs.对照组：1.36±0.1321；AgRP, Ago40: 0.52±0.03，对照组：1.49±0.27,P < 0.05)，而厌氧性可卡因和安非他明调节转录物（CART）和propropiomanocortin （POMC）升高(CART: Ago40: 1.19±0.08，对照组：0.92±0.06；POMC: Ago40: 1.49±0.17与控制:0.67±0.10,P < 0.05)。这些发现表明阿戈美拉汀通过调节食欲相关激素和下丘脑神经肽来促进体重减轻，突出了其治疗肥胖和代谢紊乱的潜力。

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来源期刊

Experimental Physiology 医学-生理学

CiteScore

5.10

自引率

3.70%

发文量

262

审稿时长

1 months

期刊介绍： Experimental Physiology publishes research papers that report novel insights into homeostatic and adaptive responses in health, as well as those that further our understanding of pathophysiological mechanisms in disease. We encourage papers that embrace the journal’s orientation of translation and integration, including studies of the adaptive responses to exercise, acute and chronic environmental stressors, growth and aging, and diseases where integrative homeostatic mechanisms play a key role in the response to and evolution of the disease process. Examples of such diseases include hypertension, heart failure, hypoxic lung disease, endocrine and neurological disorders. We are also keen to publish research that has a translational aspect or clinical application. Comparative physiology work that can be applied to aid the understanding human physiology is also encouraged. Manuscripts that report the use of bioinformatic, genomic, molecular, proteomic and cellular techniques to provide novel insights into integrative physiological and pathophysiological mechanisms are welcomed.