Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty

Heras Violeta; Manuel Castellano Juan; Fernandois Daniela; Velasco Inmaculada; Rodriguez-Vazquez Elvira; Roa Juan; Jesus Vazquez Maria; Ruiz-Pino Francisco; Rubio Matias; Pineda Rafael; Torres Encarnacion; Soledad Avendano Maria; Paredes Alfonso; Pinilla Leonor; Belsham Denise; Dieguez Carlos; Gaytan Francisco; Casals Nuria; Lopez Miguel; Tena-Sempere Manuel

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Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty

机译：中央神经酰胺信号传导介导肥胖诱导的预焦青春期

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Childhood obesity, especially in girls, is frequently bound to earlier puberty, which is linked to higher disease burden later in life. The mechanisms underlying this association remain elusive. Here we show that brain ceramides participate in the control of female puberty and contribute to its alteration in early-onset obesity in rats. Postnatal overweight caused earlier puberty and increased hypothalamic ceramide content, while pharmacological activation of ceramide synthesis mimicked the pubertal advancement caused by obesity, specifically in females. Conversely, central blockade of de novo ceramide synthesis delayed puberty and prevented the effects of the puberty-activating signal, kisspeptin. This phenomenon seemingly involves a circuit encompassing the paraventricular nucleus (PVN) and ovarian sympathetic innervation. Early-onset obesity enhanced PVN expression of SPTLC1, a key enzyme for ceramide synthesis, and advanced the maturation of the ovarian noradrenergic system. In turn, obesity-induced pubertal precocity was reversed by virogenetic suppression of SPTLC1 in the PVN. Our data unveil a pathway, linking kisspeptin, PVN ceramides, and sympathetic ovarian innervation, as key for obesity-induced pubertal precocity.

机译：儿童肥胖症，尤其是女孩，往往与青春期提前有关，这与日后更高的疾病负担有关。这种联系背后的机制仍然难以捉摸。在这里，我们表明，脑神经酰胺参与控制女性青春期，并有助于改变大鼠早发性肥胖。出生后超重导致青春期提前，下丘脑神经酰胺含量增加，而神经酰胺合成的药理学激活模拟了肥胖引起的青春期进展，尤其是女性。相反，中枢阻断从头神经酰胺合成延迟了青春期，并阻止了青春期激活信号kisspeptin的作用。这种现象似乎涉及到一个环绕脑室旁核（PVN）和卵巢交感神经支配的回路。早发性肥胖可增强神经酰胺合成关键酶SPTLC1的PVN表达，并促进卵巢去甲肾上腺素能系统的成熟。反过来，肥胖诱导的青春期早熟通过PVN中SPTLC1的病毒生成抑制而逆转。我们的数据揭示了一条连接kisspeptin、PVN神经酰胺和卵巢交感神经支配的通路，这是肥胖诱发青春期早熟的关键。

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来源
《Cell metabolism》 |2020年第6期|共25页
作者
Heras Violeta; Manuel Castellano Juan; Fernandois Daniela; Velasco Inmaculada; Rodriguez-Vazquez Elvira; Roa Juan; Jesus Vazquez Maria; Ruiz-Pino Francisco; Rubio Matias; Pineda Rafael; Torres Encarnacion; Soledad Avendano Maria; Paredes Alfonso; Pinilla Leonor; Belsham Denise; Dieguez Carlos; Gaytan Francisco; Casals Nuria; Lopez Miguel; Tena-Sempere Manuel;
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作者单位

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Chile Dept Biochem &

Mol Biol Lab Neurobiochem Fac Chem &

Pharmaceut Sci Santiago Chile;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Chile Dept Biochem &

Mol Biol Lab Neurobiochem Fac Chem &

Pharmaceut Sci Santiago Chile;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Chile Dept Biochem &

Mol Biol Lab Neurobiochem Fac Chem &

Pharmaceut Sci Santiago Chile;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Univ Toronto Dept Physiol Med Sci Bldg Toronto ON Canada;

Inst Salud Carlos III CIBER Fisiopatol Obesidad &

Nutr CIBEROBN Cordoba 14004 Spain;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

Inst Salud Carlos III CIBER Fisiopatol Obesidad &

Nutr CIBEROBN Cordoba 14004 Spain;

Inst Salud Carlos III CIBER Fisiopatol Obesidad &

Nutr CIBEROBN Cordoba 14004 Spain;

Univ Cordoba Inst Maimonides Invest Biomed Cordoba IMIBIC Dept Cell Biol Physiol &

Immunol;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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2. Central precocious puberty as a prelude to hypogonadism in a patient with Klinefelter syndrome [J] . Chunxiu Gong, Lele Li, Jiahui Chen, 儿科学（英文） . 2019,第002期
3. Central precocious puberty as a prelude of gonad dysplasia [J] . Lele Li, Chunxiu Gong 儿科学研究（英文） . 2019,第001期
4. Changing Etiological Trends in Male Precocious Puberty: Evaluation of 100 Cases with Central Precocious Puberty over the Last Decade [J] . Alikasifoglu Ayfer, Vuralli Dogus, Gonc E. Nazli, Hormone research in p?diatrics . 2015,第5期

机译：男性性早熟的病因变化趋势：近十年来中枢性性早熟的100例病例的评估
5. Utility of breast ultrasonography in the diagnostic work-up of precocious puberty and proposal of a prognostic index for identifying girls with rapidly progressive central precocious puberty. [J] . Calcaterra V, Sampaolo P, Klersy C, Ultrasound in obstetrics & gynecology: the official journal of the International Society of Ultrasound in Obstetrics and Gynecology . 2009,第1期

机译：乳房超声检查在性早熟诊断中的实用性，并提出了一种预后指标，用于识别患有快速进行性中央性早熟的女孩。
6. Prepubertal exposure to an oestrogenic mycotoxin zearalenone induces central precocious puberty in immature female rats through the mechanism of premature activation of hypothalamic kisspeptin-GPR54 signaling [J] . Yang Rong, Wang Yi-Mei, Zhang Li, Molecular and Cellular Endocrinology . 2016,第3期

机译：青春期前暴露于雌激素性霉菌毒素玉米赤霉烯酮通过下丘脑kisepteptin-GPR54信号过早激活的机制诱导未成熟雌性大鼠的中枢性早熟。
7. Association of gene mutation with central precocious puberty: A meta-analysis [C] . Minjie Zhang, Xu Yong 2011 International Conference on Remote Sensing, Environment and Transportation Engineering . 2011

机译：基因突变与中枢性性早熟的关联：一项荟萃分析
8. The effect of alpha-2-macroglobulin on dopamine concentration in corpus striatum andtrkB-mediated signal transduction and gene expression: A study on its potential role in neurodegeneration in the central nervous system [D] . Hu, Yiqun 1997

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9. A potential mechanism for the sexual dimorphism in the onset of puberty and incidence of idiopathic central precocious puberty in children: sex-specific kisspeptin as an integrator of puberty signals [O] . Suzy D. C. Bianco 2012

机译：儿童青春期发病和特发性中枢性性早熟发病率发生性二态性的潜在机制：特定性别的Kisspeptin作为青春期信号的整合者
10. A potential mechanism for the sexual dimorphism in the onset of puberty and incidence of idiopathic central precocious puberty in children: sex-specific kisspeptin as an integrator of puberty signals [O] . Suzy D. C. Bianco 2012

机译：青春期开始时性别二态性和儿童特发性中枢性性早熟发生的潜在机制：性别特异性kisspeptin作为青春期信号的整合者
11. Puberty in Corriedale, Criollo and Junin Male Sheep in the Central Sierra of Peru (Pubertad en Machos Ovinos Corriedale, Criollo y Junin en la Sierra Central del Peru) [R] . Vivanco, H. W. , Nelson, E. A. , Foote, W. C. , 1986

机译：秘鲁中部的Corriedale，Criollo和Junin公羊的青春期（pubertad en machos Ovinos Corriedale，Criollo y Junin en la sierra Central del peru）

Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty

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