A5001006911- Hypothalamic control of reproductive hormones
- Regulation of Appetite and Obesity
- Ovarian function and disorders
- Adipose Tissue and Metabolism
- Plant Reproductive Biology
- Birth, Development, and Health
- Diet and metabolism studies
- Pancreatic function and diabetes
- Growth Hormone and Insulin-like Growth Factors
- Estrogen and related hormone effects
- Metabolism, Diabetes, and Cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Reproductive Biology and Fertility
- Dietary Effects on Health
- Peroxisome Proliferator-Activated Receptors
- Neuroendocrine regulation and behavior
- Cannabis and Cannabinoid Research
- Gut microbiota and health
- Diet, Metabolism, and Disease
- Neuropeptides and Animal Physiology
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Stress Responses and Cortisol
- Hormonal Regulation and Hypertension
- Pregnancy and preeclampsia studies
- Plant Molecular Biology Research
Instituto de Salud Carlos III
2011-2024
Centro de Investigación Biomédica en Red
2008-2024
Instituto Maimónides de Investigación Biomédica de Córdoba
2011-2024
University of Córdoba
2013-2024
Hospital Universitario Reina Sofía
2012-2024
Cordoba University
2010-2021
Helmholtz Zentrum München
2016-2020
Technical University of Munich
2016
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition
2016
German Center for Diabetes Research
2016
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that operates as sensor cellular energy status and effector for its coupling to cell growth proliferation. At the hypothalamic arcuate nucleus, mTOR signaling has been recently proposed transducer leptin effects on homeostasis food intake. However, whether central also participates in metabolic regulation fertility remains unexplored. We provide herein evidence involvement control puberty onset LH secretion, likely via...
Kisspeptins (Kp) have recently emerged as master regulators of the reproductive axis and among most potent elicitors GnRH-gonadotropin secretion. Despite their paramount importance in physiology potential therapeutic implications, development Kp antagonists has remained elusive, only first compound with ability to block actions vitro vivo, namely p234, been reported. However, previous vivo studies all used acute central injections, whereas characterization effects antagonist after continuous...
Kiss1 neurons have recently emerged as a putative conduit for the metabolic gating of reproduction, with leptin being regulator hypothalamic expression. Early perturbations nutritional status are known to predispose different disorders later in life and alter timing puberty; however, potential underlying mechanisms remain poorly defined. Here we report how changes pattern postnatal feeding affect onset puberty evaluate key hormonal neuropeptide [Kiss1/kisspeptin (Kp)] alterations linked...
Glial cells perform critical functions that alter the metabolism and activity of neurons, there is increasing interest in their role appetite energy balance. Leptin, a key regulator metabolism, has previously been reported to influence glial structural proteins morphology. Here, we demonstrate metabolic status leptin also modify astrocyte-specific glutamate glucose transporters, indicating signals synaptic efficacy uptake and, ultimately, neuronal function. We found basal glucose-stimulated...
Human genetic studies have revealed that neurokinin B (NKB) and its receptor, neurokinin-3 receptor (NK3R), are essential elements for normal reproduction; however, the precise role of NKB-NK3R signaling in initiation puberty remains unknown. We investigated here regulation Tac2 Tacr3 mRNAs (encoding NKB NK3R, respectively) female rats demonstrated their hypothalamic expression is increased along postnatal maturation. At puberty, both genes were widely expressed throughout brain, including...
The hypothalamic peptide, nesfatin-1, derived from the precursor NEFA/nucleobindin 2 (NUCB2), was recently identified as anorexigenic signal, acting in a leptin-independent manner. Yet its participation regulation of other biological functions gated by body energy status remains unexplored. We show herein that NUCB2/nesfatin-1 is involved control female puberty. NUCB2/nesfatin mRNA and protein were detected at hypothalamus pubertal rats, with prominent signals lateral (LHA), paraventricular...
Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing puberty have been reported humans. These might be linked escalating prevalence childhood obesity and could deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays role energy homeostasis mediating actions leptin likely participates control reproduction. However, its...
RF-amide related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone (GnIH), have been proposed key regulators gonadotropin secretion in higher vertebrates. Yet considerable debate has arisen recently on their physiological relevance and potential mechanisms sites action. Present studies were undertaken to further characterize effects RFRP LH FSH by a combination vivo vitro approaches male female rats. Initial screening via intracerebroventricular...
Lin28 and Lin28b are related RNA-binding proteins that inhibit the maturation of miRNAs let-7 family participate in control cellular stemness early embryonic development. Considerable interest has arisen recently concerning other physiological roles Lin28/let-7 axis, including its potential involvement puberty, as suggested by genome-wide association studies functional genomics. We report herein expression profiles members rat hypothalamus during postnatal selected models altered puberty....
Nesfatin-1, product of the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as anorectic hypothalamic neuropeptide, acting in a leptin-independent manner. In addition to its central role control energy homeostasis, evidence has mounted recently that nesfatin-1 is also produced peripheral metabolic tissues, such pancreas, adipose, and gut. Moreover, been shown participate body functions gated by whole-body including puberty onset. Yet, whether, case for other neuropeptides,...
Alterations of gut microbiome have been proposed to play a role in metabolic disease, but the major determinants microbiota composition remain ill defined. Nutritional and sex hormone challenges, especially during early development, shown permanently alter adult female phenotype contribute disturbances. In this study, we implemented large-scale analyses fecal samples from groups rats sequentially subjected various obesogenic manipulations, including perturbations by means neonatal...
Attainment of reproductive capacity at puberty relies on a complex series maturational events that include sexual differentiation the brain; hormonally driven phenomenon takes place early stages development (critical period). Alterations sex steroid milieu during such critical period disrupt pubertal maturation and gonadotropic function later in life, through mechanisms remain partially unknown. Kisspeptins, products KiSS-1 gene acting via G protein-coupled receptor 54, have recently emerged...
Body energy stores and metabolic cues influence the onset of puberty. However, pubertal impact early nutritional challenges has been only fragmentarily addressed. We evaluated here consequences, in terms timing hormonal markers, various manipulations during pre- or postnatal maturation rats both sexes. Males females were submitted to gestational undernutrition (UNG) peripubertal (SUB) subnutrition raised large (LL; underfeeding) small (SL; overfeeding) litters. In addition, groups UNG, LL,...
Identification of RF-amide-related peptides (RFRP), as putative mammalian orthologs the avian gonadotropin-inhibitory hormone, has drawn considerable interest on its potential effects and mechanisms action in control gonadotropin secretion higher vertebrates. Yet, these analyses have so far relied mostly indirect approaches, while direct assessment their physiological roles been hampered by lack suitable antagonists. RF9 was recently reported a selective potent antagonist receptors for RFRP...
Abstract Neurokinin B (NKB), encoded by Tac2 in rodents, and its receptor, NK3R, have recently emerged as important regulators of reproduction; NKB has been proposed to stimulate kisspeptin output onto GnRH neurons. Accordingly, shown induce gonadotropin release several species; yet, null or even inhibitory effects also reported. The basis for these discrepant findings, well other key aspects function, remains unknown. We report here that the rat, LH responses NK3R agonist, senktide, display...
Reproduction is sensitive to insufficient body energy reserves, especially in females. Metabolic regulation of the male reproductive axis less obvious, and impact conditions persistent excess has received moderate attention. Yet, escalating prevalence obesity clinical evidence its deleterious effects on fertility have raised considerable concerns. We report here phenotypic mechanistic studies postnatal nutritional manipulations (mainly overnutrition) coupled a high-fat diet (HFD) after...
Fibroblast activation protein (FAP) is a serine protease belonging to S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported regulate degradation of FGF21, potent metabolic hormone. Using known FAP inhibitor, talabostat (TB), we explored the impact inhibition on regulation mice. To address this question evaluated pharmacology TB various mouse models including those deficient GLP1 GIP signaling. We also studied ability process FGF21...
Using long-term streptozotocin (STZ)-treated male rats, we recently proposed that defective function of hypothalamic KiSS-1 system is mechanistically relevant for central hypogonadotropism uncontrolled diabetes. However, the temporal pattern such defects and its potential contribution to disturbed gonadotropin secretion in diabetic female remain so far unexplored. To cover these issues, expression analyses hormonal tests were conducted (1 wk after STZ; short term) (4 long rats. Short-term...