Functional Obesomics
The research activity has been mainly focused on the field of Endocrinology and Nutrition. During the last 30 years this activity has been reflected in more than 450 works in international journals that have been highly cited (> 36,000 total citations,> 15000 since 2012). In general terms, this activity has been focused on the field of research into the regulatory mechanisms of growth hormone secretion and in the field of hypothalamic control of energy balance. The main focus was to uncover the dual role played by leptin and ghrelin on energy balance and neuroendocrine effects at a large with particular emphasis on pituitary hormone secretion in relation to metabolic status. The group also make important contributions in relation to the study of peripheral signals (adipokines, gastrointestinal, thyroid and gonadal hormones) on energy intake and expenditure. Currently the group is focus in the role play by different neuronal populations on the central control of energy balance and metabolic homeostasis assesing the influence of diet, ageing and gender. Some of our studies were published in high impact transdisciplinary journals such as Lancet, Nature Medicine, Physiological Reviews, Trends in Molecular Medicine, Trends in Biochemical Sciences, Trends in Pharmaceutical Sciences, EMBO Journal, Frontiers in Neuroendocrinology, Cell Metabolism, Gastroenterology, Hepatology, etc.. The Group's research activity has been financed largely through European projects of V, VI, VII PM and H2020 and national sources. Our data has aroused the interest of a large number of audiences having given lectures by invitation, among others, at the following conferences: World of endocrinology, European Endocrinology, World of Neuroendocrinology, European Neuroendocrinology, European Pharmacology, European Neuropsychopharmacology, World Physiology, European Obesity etc.
Research Lines
The research lines of the group are focused on the study of the pathophysiological mechanisms of obesity with the aim of identifying new therapeutic targets for the treatment of this pathology. The main emphasis is currently focused on the study of the reward mechanisms induced by certain foods within a European consortium (NEUROFAST). The central regulation of intermediary metabolism by CNS structures and the development of preclinical models of obesity for the evaluation of new targets/drugs are also being studied.
Selected publications
Hypothalamic AMPK-ER stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance
Chronic sympathoexcitation through loss of Vav3, a Rac1 activator, results in divergent effects on metabolic syndrome and obesity depending on diet.
Ghrelin requires p53 to stimulate lipid storage in fat and liver.
Selected Results
Figure 1: A: Effects of nutritional status on hypothalamic SIRT1Hypothalamic acetylated p53 levels after intracerebroventricular ghrelin injection (5 ug/rat) after 6 h. B: Pharmacologic blockade of SIRT1 blunts the orexigenic action of ghrelin; Effects of intracerebroventricular ghrelin injection (5 ug/rat),Ex527 (1 ug/rat), and ghrelin + Ex527 on food intake after 6 h. C: Mice lacking p53 do not respond to ghrelin injection. Effects of intracerebroventricular ghrelin injection (5 ug/mouse) on food intake after6 h in WT and p53 KO mice. D: Schematic overview summarizing our proposed model for the molecular mechanisms initiated by the activation of the ghrelin receptorleading to AMPK activation and finally to an increased feeding behavior. ROS, reactive oxygen species; CPT, carnitine palmitoyltransferase; UCP, uncoupling protein.