Childhood development (obesity and growth)
How an individual’s genetic characteristics interact with the early/neonatal and postnatal maternal environment to culminate in obesity and its secondary complications is being studied through clinical and basic approaches. Genetic studies are underway to identify gene mutations involved in monogenic obesity, identify new candidate genes and analyse polygenic and epigenetic causes of obesity. New candidate genes have been identified and are being studied, as well as genotype/phenotype interaction and ethnic influence. Metabolic studies are underway to better understand the processes involved in the development of insulin resistance and type 2 diabetes in obese children.
Metabolites that may be involved in this process have been identified and will be studied in depth. Furthermore, it seems that this process is different in men and women, even at a pre-pubescent age. This will be explored in detail. We have recently identified a new monogenic cause of human pathological growth that relates to skeletal abnormalities. The underlying cause is the involvement of the insulin-like growth factor (IGF) system, and this new syndrome will be analysed in detail for new concepts about the physiological functioning of the IGF system.
Animal models are being used to analyse how poor maternal and/or neonatal nutrition, stress or changes in specific hormones during neonatal life affect adult metabolism, with special attention focused on the differential response between males and females. Studies analysing the effect of increased levels of central leptin on insulin signalling in CNS and adipose tissue demonstrate a relationship between insulin resistance, hypothalamic inflammation and energetic homeostasis. Hypothalamic glial cells are a major research focus due to their newly recognised role in metabolic control.
We have shown that they respond to weight gain and metabolic hormones such as leptin. Our current interest includes analysis of glial responses to specific nutrients and how these might influence metabolic response to weight gain. Weight gain and abnormal circulating leptin levels have been implicated in increased susceptibility to neurodegenerative diseases, to varying degrees in men and women. Future studies are planned to determine the role of astrocytes as mediators of protective and/or detrimental responses to high-fat diet intake in neurodegeneration.
Other team members
Jefe de grupo:
Jesús Argente Oliver
Hospital Infantil Universitario Niño Jesús
| Other team members:
Argente Oliver, Jesús. Obesidad infantil grave de comienzo precoz: fundamentos metabólicos, hormonales, genéticos, genómicos y metabolómicos. PI13/02195. ISCIII. 2014-2016.
Chowen King, Julie Ann. Alteraciones cerebrales inducidas por la dieta: diferencias sexuales y mecanismos protectores de las hormonas gonadales y tibolona. BFU2014-51836-C2-2-R. MINECO. Coordinated project. 2015-2017.
Soriano-Guillén L, Corripio R, Labarta JI, Cañete R, Castro-Feijóo L, Espino R, Argente J. Central Precocious Puberty in Children Living in Spain: Incidence, Prevalence, and Influence of Adoption and Immigration. J Clin Endocrinol Metab 2010. 95: 4305-4313. FI: 6.495(Q1). PMID: 20554707. DOI: 10.1210/jc.2010-1025.
Horvath TL, Sarman B, García-Cáceres C, Enriori PJ, Sotonyi P, Shanabrough M, Borok E, Argente J, Chowen JA, Perez-Tilve D, Pfluger PT, Brönneke HS, Levin BE, Diano S, Cowley MA, Tschöp MH. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci U S A 2010. 107: 14875-14880. FI: 9.771(Q1). PMID: 20679202. DOI: 10.1073/pnas.1004282107.
Fuente-Martin, Esther, Garcia-Caceres, Cristina, Granado, Miriam, de Ceballos, Maria L., Angel Sanchez-Garrido, Miguel, Sarman, Beatrix, Liu, Zhong-Wu, Dietrich, Marcelo O., Tena-Sempere, Manuel, Argente-Arizon, Pilar, Diaz, Francisca, Argente, Jesus, Horvath, Tamas L., Chowen, Julie A. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J. Clin. Invest. 2012. 122: 3900-3913. FI: 12.812(Q1). PMID: 23064363. DOI: 10.1172/JCI64102.
Argente J, Flores R, Gutiérrez-Arumí A, Verma B, Martos-Moreno GÁ, Cuscó I, Oghabian A, Chowen JA, Frilander MJ, Pérez-Jurado LA. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency. EMBO Mol Med 2014. 6: 299-306. FI: 8.665(Q1). PMID: 24480542. DOI: 10.1002/emmm.201303573.
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J, Liu ZW, Zimmer MR, Jeong JK, Szigeti-Buck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N, Vaccarino FM, Chowen J, Diano S, Dietrich MO, Tschöp MH, Horvath TL. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat. Neurosci. 2014. 17: 908-910. FI: 16.095(Q1). PMID: 24880214. DOI: 10.1038/nn.3725.