Hypothalamic actions of estrogens in the regulation of energy and glucose homeostasis Ismael González-García, Yong Xu Reviews in Endocrine and Metabolic Disorders, 2026 Estrogens are a group of steroid hormones that exert a key role in female sexual and reproductive development and function. Produced primarily in the ovaries, estrogens influence many different aspects of physiology such as temperature homeostasis, feeding behavior, locomotor activity and glucose homeostasis by acting at the central nervous system. In particular, these endocrine factors interact with different hypothalamic nuclei in order to exert an increase in body temperature, anorectic effect, increased locomotion and improved glucose handling. Estrogenic actions can be mediated through several receptors, including the estrogen receptor-α (ERα), estrogen receptor-β (ERβ) and G protein-coupled estrogen receptor 1 (GPER1). Among these, ERα is well established to be one key receptor mediating estrogenic actions on energy balance partially through its transcriptional activity as a nuclear receptor. In addition to the transcriptional activities, E2 can also trigger rapid signaling cascades in the hypothalamus where AMPK, cAMP, PI3K, mTOR and ceramides, have all been implicated to mediate metabolic actions of E2. Moreover, E2 can induce in neurons super-fast excitations through the membrane-bound ERα. A putative membrane ER coupled to Gq (Gq-mER) has been proposed to mediate E2 actions on G protein-gated inwardly rectifying potassium GIRK, on the small conductance calcium-activated potassium (SK) currents, and on the ATP-sensitive potassium (K ATP ) currents in hypothalamic neurons. Finally, a chloride ion channel (Clic1) was recently proposed to mediate E2-induced excitation of ERα-expressing neurons in the hypothalamus. This article will review recent advances in understanding these neurobiological processes regulated by estrogens and the associated molecular mechanism.
Defective Olfactomedin-2 connects adipocyte dysfunction to obesity Aina Lluch, Jèssica Latorre, Isabel Espadas, Núria Oliveras-Cañellas, José M. Moreno-Navarrete, Estefanía Caballano-Infantes, Gitalee Sarker, Nicolás F. Malvido, Pablo Garrido-Gil, José L. Labandeira-García, Naoki Nakaya, Silvia Mora, Eduardo Chicano, Jaime López-Alcalá, María M. Malagón, Alejandro Martín-Montalvo, Birong Zhang, You Zhou, Ana I. Domingos, Miguel López, Johanna Pörschke, María Gómez-Serrano, Witold Szymanski, Johannes Graumann, Stanislav I. Tomarev, Ismael González-García, José M. Fernández-Real, Francisco J. Ortega Nature Communications, 2025 Olfactomedin-2 (OLFM2) is a pleiotropic glycoprotein emerging as a regulator of energy homeostasis. We here show the expression of OLFM2 to be adipocyte-specific and inversely associated with obesity. OLFM2 levels increase during adipogenesis and are suppressed in inflamed adipocytes. Functionally, OLFM2 deficiency impairs adipocyte differentiation, while its over-production enhances the adipogenic transformation of fat cell progenitors. Loss and gain of function experiments revealed that OLFM2 modulates key metabolic and structural pathways, including PPAR signaling, citrate cycle, fatty acid degradation, axon guidance and focal adhesion in 3T3 cell lines and primary human adipocytes. On the molecular level, OLFM2 deficiency in differentiated adipocytes predominantly downregulates genes involved in cell cycle. Extending these findings in vivo, both whole-body Olfm2 knockout and adipose-specific Olfm2 depletion in mice resulted in impaired adipose cell cycle gene expression, with the latter also displaying fat mass accretion and metabolic dysfunction. Collectively, our results underscore a critical role for OLFM2 in adipocyte biology, and support a causative link between reduced adipose OLFM2 and the pathophysiology of obesity. Olfactomedin-2 is a pleiotropic glycoprotein emerging as a regulator of energy homeostasis via the hypothalamus. The present findings functionally connect adipose-specific OLFM2 to obesity, and highlight its significance in maintaining adipocyte commitment to avoid metabolic disease.
JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism Iara Fernández-González, Oscar Freire-Agulleiro, Vitor Ferreira, María Silveira-Loureiro, Eva Rial-Pensado, Pablo Garrido-Gil, Gloria Martínez, Patricia Rada, José L. Labandeira-García, Jens Mittag, Ismael González-García, Carlos Diéguez, Rubén Nogueiras, Ángela M. Valverde, Roger J. Davis, Guadalupe Sabio, Olga Barca-Mayo, Miguel López Molecular Metabolism, 2025 Hypothalamic energy, such as AMP-activated protein kinase (AMPK), and stress sensors, such as c-Jun N-terminal kinase 1 (JNK1, also known as MAPK8) modulate whole body energy balance. While the role of AMPK in steroidogenic factor 1 (SF1) neurons of the VMH has been investigated, the relevance of JNK1 in this neuronal population has not been addressed. Here, we investigated the involvement of JNK1 SF1 on energy homeostasis. We generated mice bearing conditional JNK1 disruption through Mapk8 gene deletion in SF1 neurons ( Sf1 Cre /Jnk1 fl/fl ). Complete metabolic phenotyping, fasting/refeeding and cold challenges, as well as the central response to triiodothyronine (T3) on brown adipose tissue (BAT) thermogenesis and hepatic lipid metabolism were carried out. Sf1 Cre /Jnk1 fl/fl mice displayed decreased body weight, improved glucose tolerance, and reduced hepatic lipid levels. However, Sf1 Cre /Jnk1 fl/fl did not properly defend their temperature upon cold exposure. While central administration of T3 elicited feeding independent weight loss in both wildtype ( Jnk1 fl/fl ) and SF1 Cre /Jnk1 fl/fl mice, it did not promote hepatic lipid accretion in null animals. Our data demonstrated for the first time that JNK1 in SF1 neurons is necessary for the regulation of hepatic lipid metabolism, cold adaptation and central T3 actions. • Lack of JNK1 in SF1 neurons decreases body weight. • Lack of JNK1 in SF1 neurons improves glucose tolerance. • Lack of JNK1 in SF1 neurons impairs temperature defense upon cold. • Lack of JNK1 in SF1 neurons decreases hepatic lipid content. • Lack of JNK1 in SF1 neurons impairs the hepatic response, but not the BAT response, to central T3.
Neuroprotective effect of small extracellular vesicle-mediated targeting of AMPKα2 in cerebral ischemia Alberto Ouro, Amanda Rodríguez-Díaz, Tania López-González, Daniel Romaus-Sanjurjo, Ánxela Estévez-Salguero, Ramón Iglesias-Rey, Mariña Rodríguez-Arrizabalaga, Paola Fernández-Sanmartín, Mónica Castro-Mosquera, Manuel Debasa-Mouce, Antía Custodia, Marta Aramburu-Núñez, María Muñoz-González, Pablo Aguiar, Ismael González-García, Marc Schneeberger, Rubén Nogueiras, Carlos Diéguez, José Castillo, Tomás Sobrino, Miguel López Metabolism Clinical and Experimental, 2025
SF1-specific deletion of the energy sensor AMPKγ2 induces obesity Óscar Freire-Agulleiro, Ánxela Estévez-Salguero, Vitor Ferreira, Cassie Lynn Holleman, Julia García-Currás, Ismael González-García, Rubén Nogueiras, Manuel Tena-Sempere, Cristina García-Cáceres, Carlos Diéguez, Miguel López Molecular Metabolism, 2025 OBJECTIVE: AMP-activated protein kinase (AMPK) is a heterotrimer complex consisting of a catalytic α subunit (α1, α2) with a serine/threonine kinase domain, and two regulatory subunits, β (β1, β2) and γ (γ1, γ2, γ3), encoded by different genes. In the hypothalamus, AMPK plays a crucial role in regulating energy balance, including feeding, energy expenditure, peripheral glucose and lipid metabolism. However, most research on hypothalamic AMPK has concentrated on the catalytic subunits AMPKα1 and AMPKα2, with little focus on the regulatory subunits. METHODS: To fill this gap of knowledge, we investigated the effects of selectively deleting the regulatory isoform AMPKγ2, which is a primary "energy sensor", in steroidogenic factor 1 (SF1) neurons of the ventromedial hypothalamic nucleus (VMH). Complete metabolic phenotyping and molecular analyses in brown adipose tissue (BAT), white adipose tissue (WAT) and liver were carried out. RESULTS: Our findings reveal that, in contrast to the obesity-protective effect of the genetic deletion of AMPKα subunits, the loss of AMPKγ2 in SF1 neurons leads to a sex-independent and feeding-independent obesity-prone phenotype due to decreased thermogenesis in brown adipose tissue (BAT) and reduced browning of WAT, resulting in lower energy expenditure. Additionally, SF1-Cre AMPKγ2 mice exhibit hepatic lipid accumulation, but surprisingly maintain normal glucose homeostasis. CONCLUSIONS: Overall, these results highlight the distinct roles of AMPK subunits within the hypothalamus.
HDAC5 controls a hypothalamic STAT5b-TH axis, the sympathetic activation of ATP-consuming futile cycles and adult-onset obesity in male mice Raian E. Contreras, Tim Gruber, Ismael González-García, Sonja C. Schriever, Meri De Angelis, Noemi Mallet, Miriam Bernecker, Beata Legutko, Dhiraj Kabra, Mathias Schmidt, Matthias H. Tschöp, Ruth Gutierrez-Aguilar, Jane Mellor, Cristina García-Cáceres, Paul T. Pfluger Molecular Metabolism, 2024 With age, metabolic perturbations accumulate to elevate our obesity burden. While age-onset obesity is mostly driven by a sedentary lifestyle and high calorie intake, genetic and epigenetic factors also play a role. Among these, members of the large histone deacetylase (HDAC) family are of particular importance as key metabolic determinants for healthy ageing, or metabolic dysfunction. Here, we aimed to interrogate the role of class 2 family member HDAC5 in controlling systemic metabolism and age-related obesity under non-obesogenic conditions. Starting at 6 months of age, we observed adult-onset obesity in chow-fed male global HDAC5-KO mice, that was accompanied by marked reductions in adrenergic-stimulated ATP-consuming futile cycles, including BAT activity and UCP1 levels, WAT-lipolysis, skeletal muscle, WAT and liver futile creatine and calcium cycles, and ultimately energy expenditure. Female mice did not differ between genotypes. The lower peripheral sympathetic nervous system (SNS) activity in mature male KO mice was linked to higher dopaminergic neuronal activity within the dorsomedial arcuate nucleus (dmARC) and elevated hypothalamic dopamine levels. Mechanistically, we reveal that hypothalamic HDAC5 acts as co-repressor of STAT5b over the control of Tyrosine hydroxylase (TH) gene transactivation, which ultimately orchestrates the activity of dmARH dopaminergic neurons and energy metabolism in male mice under non-obesogenic conditions.
GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells Natália da Silva Lima, Alba Cabaleiro, Eva Novoa, Cristina Riobello, Patrick J. Knerr, Yantao He, Eva M. Esquinas-Román, Ismael González-García, Vincent Prevot, Markus Schwaninger, Carlos Dieguez, Miguel López, Timo D. Müller, Marta Varela-Rey, Jonathan D. Douros, Ruben Nogueiras Cellular and Molecular Life Sciences, 2024 The use of incretin agonists for managing metabolic dysfunction-associated steatohepatitis (MASH) is currently experiencing considerable interest. However, whether these compounds have a direct action on MASH is still under debate. This study aims to investigate whether GLP-1R/GIPR agonists act directly in hepatocytes and hepatic stellate cells (HSCs). For this, human hepatocyte and HSCs lines, as well as primary human hepatocytes and HSCs treated with Liraglutide, Acyl-GIP or the GLP-1/GIP dual agonist (MAR709) were used. We show that the concentrations of each compound, which were effective in insulin release, did not induce discernible alterations in either hepatocytes or HSCs. In hepatocytes displaying elevated fatty acid content after the treatment with oleic acid and palmitic acid, none of the three compounds reduced lipid concentration. Similarly, in HSCs activated with transforming growth factor-β (TGFb), Liraglutide, Acyl-GIP and MAR709 failed to ameliorate the elevated expression of fibrotic markers. The three compounds were also ineffective in phosphorylating CREB, which mediates insulinotropic actions, in both hepatocytes and HSCs. These findings indicate that incretin agonists have no direct actions in human hepatocytes or hepatic stellate cells, suggesting that their beneficial effects in patients with MASH are likely mediated indirectly, potentially through improvements in body weight, insulin resistance and glycemic control.
Protocol for ovariectomy and estradiol replacement in mice María Luengo-Mateos, Antía González-Vila, Ana María Torres Caldas, Ali M. Alasaoufi, Marco González-Domínguez, Miguel López, Ismael González-García, Olga Barca-Mayo STAR Protocols, 2024 Ovariectomy, involving the surgical removal of ovaries, and estradiol replacement facilitate the understanding of sexual dimorphism-related physiological changes, encompassing reproductive biology, metabolism, and hormone-related diseases. In this study, we present a protocol for conducting ovariectomy and estradiol replacement in mice. We describe steps for performing sham and ovariectomy operations, outline preoperative preparations, and provide details on postoperative care, including analgesia administration and the removal of surgical clips. Additionally, we elaborate on the procedures for performing vehicle and estradiol injections. For complete details on the use and execution of this protocol, please refer to Luengo-Mateos et al.1
Hypothalamic free fatty acid receptor-1 regulates whole-body energy balance Nathalia R.V. Dragano, Edward Milbank, Roberta Haddad-Tóvolli, Pablo Garrido-Gil, Eva Nóvoa, Marcos F. Fondevilla, Valentina Capelli, Ariane Maria Zanesco, Carina Solon, Joseane Morari, Leticia Pires, Ánxela Estevez-Salguero, Daniel Beiroa, Ismael González-García, Olga Barca-Mayo, Carlos Diéguez, Ruben Nogueiras, José L. Labandeira-García, Elisabeth Rexen Ulven, Trond Ulven, Marc Claret, Licio A. Velloso, Miguel López Molecular Metabolism, 2024 OBJECTIVE: Free fatty acid receptor-1 (FFAR1) is a medium- and long-chain fatty acid sensing G protein-coupled receptor that is highly expressed in the hypothalamus. Here, we investigated the central role of FFAR1 on energy balance. METHODS: Central FFAR1 agonism and virogenic knockdown were performed in mice. Energy balance studies, infrared thermographic analysis of brown adipose tissue (BAT) and molecular analysis of the hypothalamus, BAT, white adipose tissue (WAT) and liver were carried out. RESULTS: Pharmacological stimulation of FFAR1, using central administration of its agonist TUG-905 in diet-induced obese mice, decreases body weight and is associated with increased energy expenditure, BAT thermogenesis and browning of subcutaneous WAT (sWAT), as well as reduced AMP-activated protein kinase (AMPK) levels, reduced inflammation, and decreased endoplasmic reticulum (ER) stress in the hypothalamus. As FFAR1 is expressed in distinct hypothalamic neuronal subpopulations, we used an AAV vector expressing a shRNA to specifically knockdown Ffar1 in proopiomelanocortin (POMC) neurons of the arcuate nucleus of the hypothalamus (ARC) of obese mice. Our data showed that knockdown of Ffar1 in POMC neurons promoted hyperphagia and body weight gain. In parallel, these mice developed hepatic insulin resistance and steatosis. CONCLUSIONS: FFAR1 emerges as a new hypothalamic nutrient sensor regulating whole body energy balance. Moreover, pharmacological activation of FFAR1 could provide a therapeutic advance in the management of obesity and its associated metabolic disorders.
CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst Sebastián Zagmutt, Paula Mera, Ismael González-García, Kevin Ibeas, María del Mar Romero, Arnaud Obri, Beatriz Martin, Anna Esteve-Codina, M. Carmen Soler-Vázquez, Marianela Bastias-Pérez, Laia Cañes, Elisabeth Augé, Carme Pelegri, Jordi Vilaplana, Xavier Ariza, Jordi García, José Martinez-González, Núria Casals, Miguel López, Richard Palmiter, Elisenda Sanz, Albert Quintana, Laura Herrero, Dolors Serra Biology of Sex Differences, 2023
High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling T. Gruber, F. Lechner, C. Murat, Raian E. Contreras, E. Sanchez-Quant, V. Miok, Konstantinos Makris, O. Le Thuc, Ismael González-García, Elena García-Clavé, Ferdinand Althammer, Quirin Krabichler, Lisa M. DeCamp, Russell G Jones, Dominik Lutter, RH Williams, P. Pfluger, Timo D Müller, S. Woods, J. Pospisilik, Celia P Martinez-Jimenez, M. Tschöp, V. Grinevich, C. García-Cáceres Cell Reports, 2023
Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1 Ismael González-García, Elena García-Clavé, Alberto Cebrian-Serrano, Ophélia Le Thuc, Raian E. Contreras, Yanjun Xu, Tim Gruber, Sonja C. Schriever, Beata Legutko, Jutta Lintelmann, Jerzy Adamski, Wolfgang Wurst, Timo D. Müller, Stephen C. Woods, Paul T. Pfluger, Matthias H. Tschöp, Alexandre Fisette, Cristina García-Cáceres Cell Metabolism, 2023
Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner Luiza Maria Lutomska, Viktorian Miok, Natalie Krahmer, Ismael González García, Tim Gruber, Ophélia Le Thuc, Cahuê DB Murat, Beata Legutko, Michael Sterr, Gesine Saher, Heiko Lickert, Timo D. Müller, Siegfried Ussar, Matthias H. Tschöp, Dominik Lutter, Cristina García‐Cáceres GLIA, 2022
Olfactomedin 2 deficiency protects against diet-induced obesity Ismael González-García, Óscar Freire-Agulleiro, Naoki Nakaya, Francisco J. Ortega, Pablo Garrido-Gil, Laura Liñares-Pose, Johan Fernø, José Luis Labandeira-Garcia, Carlos Diéguez, Afia Sultana, Stanislav I. Tomarev, José Manuel Fernández-Real, Miguel López Metabolism Clinical and Experimental, 2022
BMP8 and activated brown adipose tissue in human newborns Adela Urisarri, Ismael González-García, Ánxela Estévez-Salguero, María P. Pata, Edward Milbank, Noemi López, Natalia Mandiá, Carmen Grijota-Martinez, Carlos A. Salgado, Rubén Nogueiras, Carlos Diéguez, Francesc Villarroya, José-Manuel Fernández-Real, María L. Couce, Miguel López Nature Communications, 2021
Synaptotagmin-13 is a neuroendocrine marker in brain, intestine and pancreas Marta Tarquis-Medina, Katharina Scheibner, Ismael González-García, Aimée Bastidas-Ponce, Michael Sterr, Jessica Jaki, Silvia Schirge, Cristina García-Cáceres, Heiko Lickert, Mostafa Bakhti International Journal of Molecular Sciences, 2021
Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation Edward Milbank, Nathalia R. V. Dragano, Ismael González-García, Marcos Rios Garcia, Verónica Rivas-Limeres, Liliana Perdomo, Grégory Hilairet, Francisco Ruiz-Pino, Patricia Mallegol, Donald A. Morgan, Ramón Iglesias-Rey, Cristina Contreras, Luisa Vergori, Juan Cuñarro, Begoña Porteiro, Aleix Gavaldà-Navarro, Rebecca Oelkrug, Anxo Vidal, Juan Roa, Tomás Sobrino, Francesc Villarroya, Carlos Diéguez, Rubén Nogueiras, Cristina García-Cáceres, Manuel Tena-Sempere, Jens Mittag, M. Carmen Martínez, Kamal Rahmouni, Ramaroson Andriantsitohaina, Miguel López Nature Metabolism, 2021
HYPOTHesizing about central comBAT against obesity Ismael González-García, Edward Milbank, Anxo Martinez-Ordoñez, Carlos Diéguez, Miguel López, Cristina Contreras Journal of Physiology and Biochemistry, 2020
Deletion of iRhom2 protects against diet-induced obesity by increasing thermogenesis Marina Badenes, Abdulbasit Amin, Ismael González-García, Inês Félix, Emma Burbridge, Miguel Cavadas, Francisco José Ortega, Érika de Carvalho, Pedro Faísca, Stefania Carobbio, Elsa Seixas, Dora Pedroso, Ana Neves-Costa, Luís F. Moita, José Manuel Fernández-Real, António Vidal-Puig, Ana Domingos, Miguel López, Colin Adrain Molecular Metabolism, 2020
Glucagon, GLP-1 and thermogenesis Ismael González-García, Edward Milbank, Carlos Diéguez, Miguel López, Cristina Contreras International Journal of Molecular Sciences, 2019
Ferritin regulates organismal energy balance and thermogenesis Birte Blankenhaus, Faouzi Braza, Rui Martins, Patricia Bastos-Amador, Ismael González-García, Ana Rita Carlos, Inês Mahu, Pedro Faisca, Jose Moura Nunes, Pedro Ventura, Verena Hoerr, Sebastian Weis, Joel Guerra, Silvia Cardoso, Ana Domingos, Miguel López, Miguel P. Soares Molecular Metabolism, 2019
Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress Ismael González-García, Cristina Contreras, Ánxela Estévez-Salguero, Francisco Ruíz-Pino, Benoit Colsh, Iván Pensado, Laura Liñares-Pose, Eva Rial-Pensado, Pablo B. Martínez de Morentin, Johan Fernø, Carlos Diéguez, Rubén Nogueiras, Hervé Le Stunff, Christophe Magnan, Manuel Tena-Sempere, Miguel López Cell Reports, 2018
Genetic targeting of GRP78 in the VMH improves obesity independently of food intake Laura Liñares-Pose, Eva Rial-Pensado, Ánxela Estévez-Salguero, Edward Milbank, Ismael González-García, Claudia Rodríguez, Patricia Seoane-Collazo, Noelia Martinez-Sánchez, Rubén Nogueiras, Dolores Prieto, Carlos Diéguez, Cristina Contreras, Miguel López Genes, 2018
Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance Noelia Martínez-Sánchez, Patricia Seoane-Collazo, Cristina Contreras, Luis Varela, Joan Villarroya, Eva Rial-Pensado, Xabier Buqué, Igor Aurrekoetxea, Teresa C. Delgado, Rafael Vázquez-Martínez, Ismael González-García, Juan Roa, Andrew J. Whittle, Beatriz Gomez-Santos, Vidya Velagapudi, Y.C. Loraine Tung, Donald A. Morgan, Peter J. Voshol, Pablo B. Martínez de Morentin, Tania López-González, Laura Liñares-Pose, Francisco Gonzalez, Krishna Chatterjee, Tomás Sobrino, Gema Medina-Gómez, Roger J. Davis, Núria Casals, Matej Orešič, Anthony P. Coll, Antonio Vidal-Puig, Jens Mittag, Manuel Tena-Sempere, María M. Malagón, Carlos Diéguez, María Luz Martínez-Chantar, Patricia Aspichueta, Kamal Rahmouni, Rubén Nogueiras, Guadalupe Sabio, Francesc Villarroya, Miguel López Cell Metabolism, 2017
Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance Cristina Contreras, Ismael González-García, Noelia Martínez-Sánchez, Patricia Seoane-Collazo, Jordi Jacas, Donald A. Morgan, Dolors Serra, Rosalía Gallego, Francisco Gonzalez, Núria Casals, Rubén Nogueiras, Kamal Rahmouni, Carlos Diéguez, Miguel López Cell Reports, 2014
Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK Pablo B. Martínez de Morentin, Ismael González-García, Luís Martins, Ricardo Lage, Diana Fernández-Mallo, Noelia Martínez-Sánchez, Francisco Ruíz-Pino, Ji Liu, Donald A. Morgan, Leonor Pinilla, Rosalía Gallego, Asish K. Saha, Andries Kalsbeek, Eric Fliers, Peter H. Bisschop, Carlos Diéguez, Rubén Nogueiras, Kamal Rahmouni, Manuel Tena-Sempere, Miguel López Cell Metabolism, 2014
RECENT SCHOLAR PUBLICATIONS
Hypothalamic actions of estrogens in the regulation of energy and glucose homeostasis I González-García, Y Xu Reviews in Endocrine and Metabolic Disorders, 1-13 , 2025 2025 Citations: 3
Defective Olfactomedin-2 connects adipocyte dysfunction to obesity A Lluch, J Latorre, I Espadas, N Oliveras-Cañellas, JM Moreno-Navarrete, ... Nature Communications 16 (1), 7154 , 2025 2025 Citations: 2
JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism I Fernández-González, O Freire-Agulleiro, V Ferreira, M Silveira-Loureiro, ... Molecular Metabolism 98, 102170 , 2025 2025 Citations: 5
Neuroprotective effect of small extracellular vesicle-mediated targeting of AMPKα2 in cerebral ischemia A Ouro, A Rodríguez-Díaz, T López-González, D Romaus-Sanjurjo, ... Metabolism 167, 156160 , 2025 2025 Citations: 9
SF1-specific deletion of the energy sensor AMPKγ2 induces obesity O Freire-Agulleiro, A Estevez-Salguero, V Ferreira, CL Holleman, ... Molecular Metabolism 92, 102091 , 2025 2025 Citations: 5
Ceramides in the central control of metabolism M López, C Diéguez, M Tena-Sempere, I González-García Trends in Endocrinology & Metabolism 36 (1), 11-14 , 2025 2025 Citations: 9
GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells N da Silva Lima, A Cabaleiro, E Novoa, C Riobello, PJ Knerr, Y He, ... Cellular and Molecular Life Sciences 81 (1), 468 , 2024 2024 Citations: 29
HDAC5 controls a hypothalamic STAT5b-TH axis, the sympathetic activation of ATP-consuming futile cycles and adult-onset obesity in male mice RE Contreras, T Gruber, I González-García, SC Schriever, M De Angelis, ... Molecular Metabolism 90, 102033 , 2024 2024 Citations: 2
Protocol for ovariectomy and estradiol replacement in mice M Luengo-Mateos, A González-Vila, AMT Caldas, AM Alasaoufi, ... STAR protocols 5 (1) , 2024 2024 Citations: 29
Hypothalamic free fatty acid receptor-1 regulates whole-body energy balance NRV Dragano, E Milbank, R Haddad-Tóvolli, P Garrido-Gil, E Nóvoa, ... Molecular metabolism 79, 101840 , 2024 2024 Citations: 24
High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling T Gruber, F Lechner, C Murat, RE Contreras, E Sanchez-Quant, V Miok, ... Cell reports 42 (10) , 2023 2023 Citations: 24
Astrocytic GABA in LHA is an obesity ‘thermostat’ I González-García, C García-Cáceres Nature Metabolism 5 (9), 1454-1455 , 2023 2023
Fezolinetant for menopausal hot flashes and night sweats I González-García, M López Trends in pharmacological sciences 44 (9), 635-636 , 2023 2023 Citations: 4
CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst S Zagmutt, P Mera, I González-García, K Ibeas, MM Romero, A Obri, ... Biology of sex Differences 14 (1), 14 , 2023 2023 Citations: 14
Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1 I González-García, E García-Clavé, A Cebrian-Serrano, O Le Thuc, ... Cell metabolism 35 (3), 438-455. e7 , 2023 2023 Citations: 62
Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner LM Lutomska, V Miok, N Krahmer, I González García, T Gruber, O Le Thuc, ... Glia 70 (11), 2062-2078 , 2022 2022 Citations: 34
An updated view on human neonatal thermogenesis I Gonzalez-Garcia, A Urisarri, R Nogueiras, C Dieguez, ML Couce, ... Nature Reviews Endocrinology 18 (5), 263-264 , 2022 2022 Citations: 3
Olfactomedin 2 deficiency protects against diet-induced obesity I González-García, Ó Freire-Agulleiro, N Nakaya, FJ Ortega, P Garrido-Gil, ... Metabolism 129, 155122 , 2022 2022 Citations: 18
Synaptotagmin-13 is a neuroendocrine marker in brain, intestine and pancreas M Tarquis-Medina, K Scheibner, I González-García, A Bastidas-Ponce, ... International Journal of Molecular Sciences 22 (22), 12526 , 2021 2021 Citations: 10
Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation E Milbank, NRV Dragano, I González-García, MR Garcia, ... Nature metabolism 3 (10), 1415-1431 , 2021 2021 Citations: 92
MOST CITED SCHOLAR PUBLICATIONS
Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK PBM de Morentin, I González-García, L Martins, R Lage, ... Cell metabolism 20 (1), 41-53 , 2014 2014 Citations: 519
Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance C Contreras, I González-García, N Martínez-Sánchez, P Seoane-Collazo, ... Cell reports 9 (1), 366-377 , 2014 2014 Citations: 271
Hypothalamic AMPK-ER stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance N Martinez-Sanchez, P Seoane-Collazo, C Contreras, L Varela, ... Cell metabolism 26 (1), 212-229. e12 , 2017 2017 Citations: 264
A functional link between AMPK and orexin mediates the effect of BMP8B on energy balance L Martins, P Seoane-Collazo, C Contreras, I González-García, ... Cell reports 16 (8), 2231-2242 , 2016 2016 Citations: 156
Reduction of hypothalamic endoplasmic reticulum stress activates browning of white fat and ameliorates obesity C Contreras, I González-García, P Seoane-Collazo, N Martínez-Sánchez, ... Diabetes 66 (1), 87-99 , 2017 2017 Citations: 129
Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys A Ortega-Molina, E Lopez-Guadamillas, JA Mattison, SJ Mitchell, ... Cell metabolism 21 (4), 558-570 , 2015 2015 Citations: 110
Estradiol regulates energy balance by ameliorating hypothalamic ceramide-induced ER stress I González-García, C Contreras, A Estevez-Salguero, F Ruíz-Pino, ... Cell Reports 25 (2), 413-423. e5 , 2018 2018 Citations: 98
Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation E Milbank, NRV Dragano, I González-García, MR Garcia, ... Nature metabolism 3 (10), 1415-1431 , 2021 2021 Citations: 92
Ferritin regulates organismal energy balance and thermogenesis B Blankenhaus, F Braza, R Martins, P Bastos-Amador, I González-García, ... Molecular metabolism 24, 64-79 , 2019 2019 Citations: 76
Glucagon, GLP-1 and thermogenesis I González-García, E Milbank, C Diéguez, M López, C Contreras International journal of molecular sciences 20 (14), 3445 , 2019 2019 Citations: 64
Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1 I González-García, E García-Clavé, A Cebrian-Serrano, O Le Thuc, ... Cell metabolism 35 (3), 438-455. e7 , 2023 2023 Citations: 62
Pregnancy induces resistance to the anorectic effect of hypothalamic malonyl-CoA and the thermogenic effect of hypothalamic AMPK inhibition in female rats PB Martinez de Morentin, R Lage, I González-García, F Ruíz-Pino, ... Endocrinology 156 (3), 947-960 , 2015 2015 Citations: 61
Insulin action on astrocytes: From energy homeostasis to behaviour I González‐García, T Gruber, C García‐Cáceres Journal of neuroendocrinology 33 (4), e12953 , 2021 2021 Citations: 59
Olanzapine depot exposure in male rats: dose-dependent lipogenic effects without concomitant weight gain J Fernø, KM Ersland, IH Duus, I González-García, KO Fossan, RK Berge, ... European Neuropsychopharmacology 25 (6), 923-932 , 2015 2015 Citations: 50
BMP8 and activated brown adipose tissue in human newborns A Urisarri, I González-García, Á Estévez-Salguero, MP Pata, E Milbank, ... Nature Communications 12 (1), 5274 , 2021 2021 Citations: 49
Estradiol regulation of brown adipose tissue thermogenesis I González-García, M Tena-Sempere, M López Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity … , 2017 2017 Citations: 49
Hypothalamic astrocytes as a specialized and responsive cell population in obesity I González-García, C García-Cáceres International journal of molecular sciences 22 (12), 6176 , 2021 2021 Citations: 42
mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol I González-García, PBM de Morentin, Á Estévez-Salguero, C Contreras, ... Journal of Endocrinology 238 (3), 177-186 , 2018 2018 Citations: 36
Hypothalamic lipids: key regulators of whole body energy balance I González-García, J Fernø, C Diéguez, R Nogueiras, M López Neuroendocrinology 104 (4), 398-411 , 2017 2017 Citations: 36
Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner LM Lutomska, V Miok, N Krahmer, I González García, T Gruber, O Le Thuc, ... Glia 70 (11), 2062-2078 , 2022 2022 Citations: 34
