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Characterization of metabolic phenotypes of mice lacking GPR61, an orphan G-protein coupled receptor.

机译:缺乏孤儿G蛋白偶联受体GPR61的小鼠的代谢表型的表征。

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AIMS: GPR61 is an orphan G protein-coupled receptor whose function remains unknown. The purpose of the present study is to elucidate the importance of GPR61 in metabolism by characterization of GPR61-deficient mice. MAIN METHODS: Male GPR61-deficient mice were characterized regarding various metabolic parameters, including food intake, body weight, oxygen consumption, body temperature, locomotor activity, and in a pair feeding study. Hypothalamic gene expression was analyzed using real-time quantitative RT-PCR. KEY FINDINGS: GPR61-deficient mice exhibited marked hyperphagia and heavier body weight than wild-type mice. Hyperphagia of GPR61-deficient mice was observed before the differences in body weight became apparent between the genotypes. When body weight difference did become apparent between genotypes, increases in visceral fat pad weight, liver weight, liver triglyceride (TG) content, plasma leptin, and plasma insulin were observed in GPR61-deficient mice, suggesting that GPR61 deficiency caused obesity associated with hyperphagia. Oxygen consumption, body temperature, and locomotor activity were not significantly different between GPR61-deficient and wild-type mice. Pair-fed GPR61-deficient mice had a greater fat mass than wild-type mice despite comparable body weight in both genotypes. The mRNA levels of proopiomelanocortin (POMC) and brain-derived neurotropic factor (BDNF) in the hypothalamus of GPR61-deficient mice were significantly lower than those of wild-type mice. SIGNIFICANCE: GPR61-deficient mice exhibited obesity associated with hyperphagia. These findings suggest that GPR61 is involved in the regulation of food intake and body weight, and may be of importance when considering GPR61 as a therapeutic target for obesity or eating disorders.
机译:目的:GPR61是一种孤儿G蛋白偶联受体,其功能尚不清楚。本研究的目的是通过鉴定缺乏GPR61的小鼠来阐明GPR61在代谢中的重要性。主要方法:雄性GPR61缺陷型小鼠的特征在于各种代谢参数,包括食物摄入,体重,耗氧量,体温,运动能力以及成对喂养研究。使用实时定量RT-PCR分析下丘脑基因表达。主要发现:GPR61缺陷型小鼠比野生型小鼠表现出明显的食欲亢进和体重增加。在基因型之间体重差异变得明显之前,已观察到GPR61缺陷型小鼠的吞噬过多。当基因型之间的体重差异确实变得明显时,在缺乏GPR61的小鼠中观察到内脏脂肪垫重量,肝脏重量,肝甘油三酯(TG)含量,血浆瘦素和血浆胰岛素的增加,表明GPR61缺乏引起肥胖与食欲亢进有关。 GPR61缺乏和野生型小鼠之间的耗氧量,体温和运动能力无明显差异。配对喂养的GPR61缺陷型小鼠的脂肪量大于野生型小鼠,尽管两种基因型的体重均相当。 GPR61缺陷型小鼠下丘脑中proopiomelanocortin(POMC)和脑源性神经营养因子(BDNF)的mRNA水平显着低于野生型小鼠。意义:GPR61缺陷型小鼠表现出与食欲亢进相关的肥胖。这些发现表明,GPR61参与食物摄入和体重的调节,并且在将GPR61视为肥胖或进食障碍的治疗目标时可能很重要。

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