Our team is consolidated group at IMIBIC, currently composed of 27 members, including 14 posdoctoral researchers, 9 predoctoral researchers and 4 technicians. We are a basic/translational group, aiming to explore the pathophysiological basis of the complex interactions between key bodily functions, such as those controlling body weight, metabolism, puberty and reproduction.
While a substantial component of our research deals with the investigation of physiological and molecular mechanisms and their contribution to disease, in the areas of our interest, we have recently undertaken also a number of more clinically-oriented projects with the overall goal of translating the basic knowledge stemming from our research activity into clinical practice. The results of our research may advance in particular the definition of better tools and markers for the diagnosis, stratification and management of highly prevalent metabolic and reproductive disorders, ranging from obesity to altered puberty, polycystic ovary syndrome and infertility. We are funded by competitive projects from regional, national and European agencies, as well as by cooperative agreements with biotech and pharma companies.
Our group collaborates with numerous groups within IMIBIC, Spain and internationally, which help us to deploy an ambitious research program covering a wide range of topics and activities within the area of hormonal regulation of energy balance, puberty and reproduction. As demonstration of active interaction and networking, our group is currently cooperating with other IMIBIC research groups in three different competitive projects, coordinating one of the nodes of the Spanish Network for Research in Obesity & Nutrition (CIBEROBN), and hold long-lasting and productive collaborations with reference groups in Finland and other countries in Europe and the USA.
Líneas de Investigación
Our team aims to unveil novel central mechanisms for the dynamic control of puberty, as key maturational event, and reproduction. Notably, prevalence of pubertal and reproductive disorders is increasing due to as yet unknown mechanisms. We are particularly focusing on the characterization of the roles of neuropeptide pathways (e.g. kisspeptins) as potential druggable targets, as well as novel molecular mechanisms (e.g. epigenetics and microRNAs).
There is strong evidence that nutritional and metabolic cues markedly influence the age of puberty and fertility. The translational implications of such phenomenon are high, since obesity has been blamed as one of the major causes for the trends of perturbed puberty and increasing infertility rates. Yet, the underlying mechanisms remain largely unknown. Our group is devoted to identify novel pathways and mechanisms whereby metabolic signals participate in the precise control of the systems governing puberty and reproduction, with the ultimate aim of providing valuable pathophysiological knowledge that may serve to set more rational strategies for the management of pubertal and reproductive disorders.
By a combination of preclinical and clinical studies, our group investigates both the mechanisms and consequences of gonadal dysfunction associated to metabolic diseases, such as obesity and diabetes. The ultimate aim of this research line is to unveil how obesity and other metabolic pathologies perturb the function of the reproductive axis, thereby resulting in insufficient secretion of sex steroid hormones, and to what extent impaired sex hormone milieu predisposes to or aggravates the metabolic complications of obesity.
Our team is applying high-throughput analytical techniques to clinical samples in order to identify novel biomarkers of common reproductive pathologies, such as polycystic ovary syndrome (PCOS), endometriosis, perturbed puberty and obesity-associated hypogonadism. The ultimate aim is to define novel tools for better diagnosis, prognosis and stratification of patients of these prevalent diseases.
CIBERobn - Physiopathology of Obesity and Nutrition
ESE - European Society of Endocrinology - Theme Area: Reproductive Endocrinology
FiDiPro Program – Finnish Academy
PAIDI BIO-310 - Energy balance and reproductive function
- energy sensors
- polycystic ovary syndrome
Heras V, Sangiao-Alvarellos S, Manfredi-Lozano M, Sanchez-Tapia MJ, Ruiz-Pino F, Roa J, Lara-Chica M, Morrugares-Carmona R, Jouy N, Abreu AP, Prevot V, Belsham D, Vazquez MJ, Calzado MA, Pinilla L, Gaytan F, Latronico AC, Kaiser UB, Castellano JM, Tena-Sempere M 2019 Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3. PLoS Biology 17(11):e3000532.
Ruiz-Pino F, Miceli D, Franssen D, Vazquez MJ, Farinetti A, Castellano JM, Panzica G, Tena-Sempere M 2019 Environmentally Relevant Perinatal Exposures to Bisphenol A Disrupt Postnatal Kiss1/NKB Neuronal Maturation and Puberty Onset in Female Mice. Environmental Health Perspectives 127(10):107011
Romero-Ruiz A, Avendaño MS, Dominguez F, Lozoya T, Molina-Abril H, Sangiao-Alvarellos S, Gurrea M, Lara-Chica M, Fernandez-Sanchez M, Torres-Jimenez E, Perdices-Lopez C, Abbara A, Steffani L, Calzado MA, Dhillo WS, Pellicer A, Tena-Sempere M. 2019. Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications. American Journal Obstetrics & Gynecology 220(5):480.
Roa J, Barroso A, Ruiz-Pino F, Vázquez MJ, Seoane-Collazo P, Martínez-Sanchez N, García-Galiano D, Ilhan T, Pineda R, León S, Manfredi-Lozano M, Heras V, Poutanen M, Castellano JM, Gaytan F, Diéguez C, Pinilla L, López M, Tena-Sempere M. 2018. Metabolic regulation of female puberty via hypothalamic AMPK-kisspeptin signaling. Proceedings National Academy Sciences USA 115(45):E10758-E10767
Vazquez MJ, Toro CA, Castellano JM, Ruiz-Pino F, Roa J, Beiroa D, Heras V, Velasco I, Dieguez C, Pinilla L, Gaytan F, Nogueiras R, Bosch MA, Rønnekleiv OK, Lomniczi A, Ojeda SR, Tena-Sempere M. 2018. SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression. Nature Communications 9:4194
Seoane-Collazo P, Roa J, Rial-Pensado E, Liñares-Pose L, Beiroa D, Ruíz-Pino F, López-González T, Morgan DA, Pardavila JÁ, Sánchez-Tapia MJ, Martínez-Sánchez N, Contreras C, Fidalgo M, Diéguez C, Coppari R, Rahmouni K, Nogueiras R, Tena-Sempere M, López M. 2018. SF1-Specific AMPKα1 Deletion Protects Against Diet-Induced Obesity. Diabetes. 67(11):2213-2226.
Avendaño MS, Vazquez MJ, Tena-Sempere M. 2017. Disentangling puberty: novel neuro-endocrine pathways and mechanisms for the control of mammalian puberty. Human Reproduction Update 23: 737-763.
Manfredi-Lozano M, Roa J, Ruiz-Pino F, Piet R, Garcia-Galiano D, Pineda R, Zamora A, Leon S, Sanchez-Garrido MA, Romero-Ruiz A, Dieguez C, Vazquez MJ, Herbison AE, Pinilla L, Tena-Sempere M. 2016. Defining a novel leptin-melanocortin-kisspeptin path-way involved in the metabolic control of puberty. Molecular Metabolism 5: 844-857.
Messina A, Langlet F, Chachlaki K, Roa J, Rasika S, Jouy N, Gallet S, Gaytan F, Parkash J, Tena-Sempere M, Giacobini P, Prevot V. 2016. A microRNA switch regulates the rise in hypothalamic GnRH production before puberty. Nature Neuroscience 19: 835-844.
Lopez M, Tena-Sempere M. 2015. Estrogens and the control of energy balance: A brain perspective. Trends Endocrinol Metab 26: 411-421.
Martínez de Morentin PB, González-García I, Martíns L, Lage R, Fernández-Mallo D, Martínez-Sánchez N, Ruíz-Pino F, Liu J, Morgan DA, Pinilla L, Gallego R, Saha AK, Kalsbeek A, Fliers E, Bisschop PH, Diéguez C, Nogueiras R, Rahmouni K, Tena-Sempere M, López M. 2014. Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metabolism 20: 41-53.
Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. 2012. Kisspeptins and reproduction: Physiological roles and regulatory mechanisms. Physiological Reviews 92: 1235-1316.
Navarro VM, Ruiz-Pino F, Sánchez-Garrido MA, García-Galiano D, Hobbs SJ, Manfredi-Lozano M, León S, Sangiao-Alvarellos S, Castellano JM, Clifton DK, Pinilla L, Steiner RA, Tena-Sempere M. 2012. Role of neurokinin B in the control of female puberty and its control by metabolic status. Journal of Neuroscience 32: 2388-2397.
García-Galiano D, Navarro VM, Roa J, Ruiz-Pino F, Sánchez-Garrido MA, Pineda R, Castellano JM, Romero M, Aguilar E, Gaytán F, Diéguez C, Pinilla L, Tena-Sempere M. 2010. The anorexigenic neuropeptide, Nesfatin-1, is indispensable for normal puberty onset in the female rat. Journal of Neuroscience 30: 7783-7792.