Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty

Aksglaede, 2009, Age at puberty and the emerging obesity epidemic, PLoS One, 4, e8450, 10.1371/journal.pone.0008450

Aksglaede, 2009, Recent decline in age at breast development: the Copenhagen Puberty Study, Pediatrics, 123, e932, 10.1542/peds.2008-2491

Auer-Grumbach, 2013, Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype, Eur. J. Med. Genet., 56, 266, 10.1016/j.ejmg.2013.02.002

Avendaño, 2017, Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty, Hum. Reprod. Update, 23, 737, 10.1093/humupd/dmx025

Barton, 2012, Childhood obesity: a life-long health risk, Acta Pharmacol. Sin., 33, 189, 10.1038/aps.2011.204

Bikman, 2011, Ceramides as modulators of cellular and whole-body metabolism, J. Clin. Invest., 121, 4222, 10.1172/JCI57144

Borg, 2012, Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice, J. Physiol., 590, 4377, 10.1113/jphysiol.2012.233288

Campana, 2018, Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats, Mol. Metab., 8, 23, 10.1016/j.molmet.2017.10.013

Caron, 2012, Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function, J. Neurosci., 32, 11486, 10.1523/JNEUROSCI.6074-11.2012

Castellano, 2013, Metabolic regulation of kisspeptin, Adv. Exp. Med. Biol., 784, 363, 10.1007/978-1-4614-6199-9_17

Castellano, 2016, Animal modeling of early programming and disruption of pubertal maturation, Endocr. Dev., 29, 87, 10.1159/000438877

Castellano, 2016, Metabolic control of female puberty: potential therapeutic targets, Expert Opin. Ther. Targets, 20, 1181, 10.1080/14728222.2016.1212015

Castellano, 2005, Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition, Endocrinology, 146, 3917, 10.1210/en.2005-0337

Castellano, 2006, Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat, Mol. Cell. Endocrinol., 257-258, 75, 10.1016/j.mce.2006.07.002

Castellano, 2011, Early metabolic programming of puberty onset: impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system, Endocrinology, 152, 3396, 10.1210/en.2010-1415

Cesario, 2007, Precocious puberty: a comprehensive review of literature, J. Obstet. Gynecol. Neonatal Nurs., 36, 263, 10.1111/j.1552-6909.2007.00145.x

Chaurasia, 2015, Ceramides - lipotoxic inducers of metabolic disorders, Trends Endocrinol. Metab., 26, 538, 10.1016/j.tem.2015.07.006

Chehab, 2014, 20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors, J. Endocrinol., 223, T37, 10.1530/JOE-14-0413

Cheung, 1997, Leptin is a metabolic gate for the onset of puberty in the female rat, Endocrinology, 138, 855, 10.1210/endo.138.2.5054

Contreras, 2014, Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance, Cell Rep., 9, 366, 10.1016/j.celrep.2014.08.057

Cote, 2013, Childhood obesity and cardiovascular dysfunction, J. Am. Coll. Cardiol., 62, 1309, 10.1016/j.jacc.2013.07.042

Cruciani-Guglielmacci, 2017, Brain ceramide metabolism in the control of energy balance, Front Physiol., 8, 787, 10.3389/fphys.2017.00787

Day, 2015, Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study, Sci. Rep., 5, 11208, 10.1038/srep11208

De Leonibus, 2014, Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls, Pediatr. Obes., 9, 292, 10.1111/j.2047-6310.2013.00176.x

de Onis, 2010, Global prevalence and trends of overweight and obesity among preschool children, Am. J. Clin. Nutr., 92, 1257, 10.3945/ajcn.2010.29786

Dobrowsky, 1992, Ceramide stimulates a cytosolic protein phosphatase, J. Biol. Chem., 267, 5048, 10.1016/S0021-9258(18)42727-5

Draper, 2011, Discovery and evaluation of inhibitors of human ceramidase, Mol. Cancer Ther., 10, 2052, 10.1158/1535-7163.MCT-11-0365

Dumont, 2015, Role of anti-Müllerian hormone in pathophysiology, diagnosis and treatment of polycystic ovary syndrome: a review, Reprod. Biol. Endocrinol., 13, 137, 10.1186/s12958-015-0134-9

Elks, 2013, Age at menarche and type 2 diabetes risk: the EPIC-InterAct study, Diabetes Care, 36, 3526, 10.2337/dc13-0446

Fernández-Fernández, 2005, Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat, Endocrinology, 146, 3018, 10.1210/en.2004-1622

Fiedler, 2006, Cold stress induces metabolic activation of thyrotrophin-releasing hormone-synthesising neurones in the magnocellular division of the hypothalamic paraventricular nucleus and concomitantly changes ovarian sympathetic activity parameters, J. Neuroendocrinol., 18, 367, 10.1111/j.1365-2826.2006.01427.x

Fucho, 2017, Ceramides and mitochondrial fatty acid oxidation in obesity, FASEB J., 31, 1263, 10.1096/fj.201601156R

Gao, 2011, Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding, Proc. Natl. Acad. Sci. USA, 108, 9691, 10.1073/pnas.1103267108

García-Galiano, 2012, Sex steroids and the control of the Kiss1 system: developmental roles and major regulatory actions, J. Neuroendocrinol., 24, 22, 10.1111/j.1365-2826.2011.02230.x

Garrido, 2018, Effects of sympathectomy on ovarian follicular development and steroid secretion, Reproduction, 155, 173, 10.1530/REP-17-0318

Gaytan, 2017, Development and validation of a method for precise dating of female puberty in laboratory rodents: the puberty ovarian maturation score (Pub-Score), Sci. Rep., 7, 46381, 10.1038/srep46381

Gerendai, 1998, Neuronal labeling in the rat brain and spinal cord from the ovary using viral transneuronal tracing technique, Neuroendocrinology, 68, 244, 10.1159/000054372

Golub, 2008, Public health implications of altered puberty timing, Pediatrics, 121, S218, 10.1542/peds.2007-1813G

González-García, 2018, Estradiol regulates energy balance by ameliorating hypothalamic ceramide-induced ER stress, Cell Rep., 25, 413, 10.1016/j.celrep.2018.09.038

Hajduch, 2001, Ceramide impairs the insulin-dependent membrane recruitment of protein kinase B leading to a loss in downstream signalling in L6 skeletal muscle cells, Diabetologia, 44, 173, 10.1007/s001250051596

Herbison, 2016, Control of puberty onset and fertility by gonadotropin-releasing hormone neurons, Nat. Rev. Endocrinol., 12, 452, 10.1038/nrendo.2016.70

Herman-Giddens, 2012, Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network, Pediatrics, 130, e1058, 10.1542/peds.2011-3291

Holland, 1991, Gonadotropin-independent precocious puberty, Endocrinol. Metab. Clin. North Am., 20, 191, 10.1016/S0889-8529(18)30288-3

Kauli, 2000, Delayed growth and puberty in patients with Gaucher disease type 1: natural history and effect of splenectomy and/or enzyme replacement therapy, Isr. Med. Assoc. J., 2, 158

Kirilov, 2013, Dependence of fertility on kisspeptin-Gpr54 signaling at the GnRH neuron, Nat. Commun., 4, 2492, 10.1038/ncomms3492

Lakshman, 2009, Early age at menarche associated with cardiovascular disease and mortality, J. Clin. Endocrinol. Metab., 94, 4953, 10.1210/jc.2009-1789

Lansdown, 2012, The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?, Clin. Endocrinol. (Oxf.), 77, 791, 10.1111/cen.12003

Lara, 1990, The gene encoding nerve growth factor is expressed in the immature rat ovary: effect of denervation and hormonal treatment, Endocrinology, 126, 357, 10.1210/endo-126-1-357

Lara, 1990, Involvement of nerve growth factor in female sexual development, Endocrinology, 126, 364, 10.1210/endo-126-1-364

Lara, 2002, Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: studies on norepinephrine release, Microsc. Res. Tech., 59, 495, 10.1002/jemt.10229

Lee, 2007, Weight status in young girls and the onset of puberty, Pediatrics, 119, e624, 10.1542/peds.2006-2188

León, 2016, Direct actions of kisspeptins on GnRH neurons permit attainment of fertility but are insufficient to fully preserve gonadotropic axis activity, Sci. Rep., 6, 19206, 10.1038/srep19206

Lie, 2013, Effect of a postnatal high-fat diet exposure on puberty onset, estrous cycle regularity, and kisspeptin expression in female rats, Reprod. Biol., 13, 298, 10.1016/j.repbio.2013.08.001

Lloyd, 2012, Childhood obesity and risk of the adult metabolic syndrome: a systematic review, Int. J. Obes., 36, 1, 10.1038/ijo.2011.186

Lobstein, 2004, Obesity in children and young people: a crisis in public health, Obes. Rev., 5, 4, 10.1111/j.1467-789X.2004.00133.x

Lookingland, 1991, 3-Methoxy-4-hydroxyphenylethyleneglycol concentrations in discrete hypothalamic nuclei reflect the activity of noradrenergic neurons, Brain Res., 559, 82, 10.1016/0006-8993(91)90289-8

López, 2010, Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance, Nat. Med., 16, 1001, 10.1038/nm.2207

Mahfouz, 2014, Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models: a mechanistic insight, PLoS One, 9, e101865, 10.1371/journal.pone.0101865

Manfredi-Lozano, 2016, Defining a novel leptin-melanocortin-kisspeptin pathway involved in the metabolic control of puberty, Mol. Metab., 5, 844, 10.1016/j.molmet.2016.08.003

Manfredi-Lozano, 2018, Connecting metabolism and gonadal function: Novel central neuropeptide pathways involved in the metabolic control of puberty and fertility, Front. Neuroendocrinol., 48, 37, 10.1016/j.yfrne.2017.07.008

Marraudino, 2017, Kisspeptin innervation of the hypothalamic paraventricular nucleus: sexual dimorphism and effect of estrous cycle in female mice, J. Anat., 230, 775

Martínez de Morentin, 2014, Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK, Cell Metab., 20, 41, 10.1016/j.cmet.2014.03.031

Martínez-Sánchez, 2017, Hypothalamic AMPK-ER stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance, Cell Metab., 26, 212, 10.1016/j.cmet.2017.06.014

Martini, 2006, Comparative analysis of the effects of ghrelin and unacylated ghrelin on luteinizing hormone secretion in male rats, Endocrinology, 147, 2374, 10.1210/en.2005-1422

McCartney, 2009, Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls, J. Clin. Endocrinol. Metab., 94, 56, 10.1210/jc.2008-1252

Navarro, 2004, Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54, J. Physiol., 561, 379, 10.1113/jphysiol.2004.072298

Navarro, 2006, Novel role of 26RFa, a hypothalamic RFamide orexigenic peptide, as putative regulator of the gonadotropic axis, J. Physiol., 573, 237, 10.1113/jphysiol.2006.106856

Newton, 2015, Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy, Exp. Cell Res., 333, 195, 10.1016/j.yexcr.2015.02.025

Nikolova-Karakashian, 2010, Ceramide in stress response, Adv. Exp. Med. Biol., 688, 86, 10.1007/978-1-4419-6741-1_6

Ogden, 2012, Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010, JAMA, 307, 483, 10.1001/jama.2012.40

Ojeda, 1989, Role of the sympathetic nervous system in the regulation of ovarian function, 26

Ojeda, 2006, Puberty in the rat, 2061

Ojeda, 2010, New concepts on the control of the onset of puberty, Endocr. Dev., 17, 44, 10.1159/000262527

Pavone, 1986, Niemann-Pick disease type B: clinical signs and follow-up of a new case, J. Inherit. Metab. Dis., 9, 73, 10.1007/BF01813906

Paxinos, 2006

Pinilla, 2011, Characterization of the reproductive effects of the anorexigenic VGF-derived peptide TLQP-21: in vivo and in vitro studies in male rats, Am. J. Physiol. Endocrinol. Metab., 300, E837, 10.1152/ajpendo.00598.2010

Pinilla, 2012, Kisspeptins and reproduction: physiological roles and regulatory mechanisms, Physiol. Rev., 92, 1235, 10.1152/physrev.00037.2010

Ramírez, 2013, Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin, Diabetes, 62, 2329, 10.2337/db12-1451

Reinehr, 2019, Is there a causal relationship between obesity and puberty?, Lancet Child Adolesc. Health, 3, 44, 10.1016/S2352-4642(18)30306-7

Ricu, 2008, Functional development of the ovarian noradrenergic innervation, Endocrinology, 149, 50, 10.1210/en.2007-1204

Roa, 2009, The mammalian target of rapamycin as novel central regulator of puberty onset via modulation of hypothalamic Kiss1 system, Endocrinology, 150, 5016, 10.1210/en.2009-0096

Roa, 2010, Metabolic control of puberty onset: new players, new mechanisms, Mol. Cell. Endocrinol., 324, 87, 10.1016/j.mce.2009.12.018

Roa, 2018, Metabolic regulation of female puberty via hypothalamic AMPK-kisspeptin signaling, Proc. Natl. Acad. Sci. USA, 115, E10758, 10.1073/pnas.1802053115

Rosenfield, 2007, Clinical review: Identifying children at risk for polycystic ovary syndrome, J. Clin. Endocrinol. Metab., 92, 787, 10.1210/jc.2006-2012

Sanchez-Garrido, 2013, Metabolic control of puberty: roles of leptin and kisspeptins, Horm. Behav., 64, 187, 10.1016/j.yhbeh.2013.01.014

Smith, 2012, Preweaning over- and underfeeding alters onset of puberty in the rat without affecting kisspeptin, Biol. Reprod., 86, 145, 10.1095/biolreprod.111.097758

Speiser, 2005, Childhood obesity, J. Clin. Endocrinol. Metab., 90, 1871, 10.1210/jc.2004-1389

Stener-Victorin, 2020, Animal models to understand the etiology and pathophysiology of polycystic ovary syndrome, Endocr. Rev., 41, 538, 10.1210/endrev/bnaa010

Takumi, 2015, Maternal high-fat diet during lactation increases Kiss1 mRNA expression in the arcuate nucleus at weaning and advances puberty onset in female rats, Neurosci. Res., 100, 21, 10.1016/j.neures.2015.06.004

Terasawa, 2001, Neurobiological mechanisms of the onset of puberty in primates, Endocr. Rev., 22, 111

True, 2011, Characterisation of arcuate nucleus kisspeptin/neurokinin B neuronal projections and regulation during lactation in the rat, J. Neuroendocrinol., 23, 52, 10.1111/j.1365-2826.2010.02076.x

Turpin-Nolan, 2020, The role of ceramides in metabolic disorders: when size and localization matters, Nat. Rev. Endocrinol., 16, 224, 10.1038/s41574-020-0320-5

Ullah, 2017, Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: a novel model of obesity and puberty, Front. Med., 11, 266, 10.1007/s11684-017-0530-y

Vazquez, 2018, SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression, Nat. Commun., 9, 4194, 10.1038/s41467-018-06459-9

Velie, 2005, Lifetime reproductive and anthropometric risk factors for breast cancer in postmenopausal women, Breast Dis., 24, 17, 10.3233/BD-2006-24103

Wolfe, 2014, The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1), Front. Neuroendocrinol., 35, 558, 10.1016/j.yfrne.2014.05.007