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Molecular Medicine Programme | Obesity

Functional Obesomics

Carlos Diéguez González
Group Leader | Full Professor
Lab: P0L3
Field of knowledge

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.


Pamela Lear
Assistant professor


María del Sol Abella Fernández
Research Specialist Technician

Selected publications

Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake
Romero-Pico, Amparo; Sanchez-Rebordelo, Estrella; Imbernon, Monica; Gonzalez-Touceda, David; Folgueira, Cintia; Senra, Ana; Ferno, Johan; Blouet, Clemence; Cabrera, Roberto; van Gestel, Margriet; Adan, Roger A.; Lopez, Miguel; Maldonado, Rafael; Nogueiras, Ruben; Dieguez, Carlos

Food Addiction and Binge Eating: Lessons Learned from Animal Models.

Novelle MG, Diéguez C.

Hypothalamic AMPK-ER stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance

Martínez-Sánchez N, Seoane-Collazo P, Contreras C, Varela L, Villarroya J, Rial-Pensado E, Buqué X, Aurrekoetxea I, Delgado TC, Vázquez-Martínez R, González-García I, Roa J, Whittle AJ, Gomez-Santos B, Velagapudi V, Tung YCL, Morgan DA, Voshol PJ, Martínez de Morentin PB, López-González T, Liñares-Pose L, Gonzalez F, Chatterjee K, Sobrino T, Medina-Gómez G, Davis RJ, Casals N, Orešič M, Coll AP, Vidal-Puig A, Mittag J, Tena-Sempere M, Malagón MM, Diéguez C, Martínez-Chantar ML, Aspichueta P, Rahmouni K, Nogueiras R, Sabio G, Villarroya F & López M

Chronic sympathoexcitation through loss of Vav3, a Rac1 activator, results in divergent effects on metabolic syndrome and obesity depending on diet.

Menacho-Márquez M, Nogueiras R, Fabbiano S, Sauzeau V, Al-Massadi O, Diéguez C, Bustelo XR.

Ghrelin requires p53 to stimulate lipid storage in fat and liver.

Porteiro B, Díaz-Ruíz A, Martínez G, Senra A, Vidal A, Serrano M, Gualillo O, López M, Malagón MM, Diéguez C, Nogueiras R.

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.


National project(s)

Estudios de SIRT3 sobre las vías homeostáticas y hedónicas relacionadas con la obesidad- RETOS JI...
REF: PID2020-114350RJ-I00Duration: -
PI: María del Mar Quiñones Pérez
Consolidación 2021 GRC GI-1233 - Grupo de Investigaciones Biomédicas - GIB
REF: ED431C 2021/23Duration: -
PI: Carlos Diéguez González


Centro de Investigación Biomédica en Red: Fisiopatología de la Obesidad y Nutrición
Red Temática Española de Descubrimiento de Fármacos (REDEFAR)


Use of p53 inhibitors for reducing food intake and lowering body weight
Aplication Nº: WO2012ES70111 20120223
Method for inhibiting appetite
Aplication Nº: ES20110031311 20110728
Isolation of multipotent hypophysary cells and in vitro differentiation thereof
Aplication Nº: WO2009ES70530 20091125
Using RSTN for body weight reduction
Aplication Nº: ES20080001306 20080506
Methods of using up-regulators of the expression of p53 and/or down-regulators or inhibitors of the expression of p63 for the treatment of NAFLD (Non-alcoholic fatty liver disease) and/or NASH (non-alcoholic steatohepatitis)
Aplication Nº: EP3366296 B1