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Mechanisms of Disease

Neuroendocrine Regulation of Metabolism (NeuRoMet)

Ismael González García
Group Leader | Ramón y Cajal Researcher
ismael.gonzalez@usc.es
 
Lab: P0L1
Field of knowledge

The overall aim of our research is to unravel the neurocircuits implicated in the control of metabolism, their molecular mechanisms as well as their hormonal effectors. 

Our work is focused on the hypothalamic regulation of energy homeostasis with specific interest in the central actions of estrogens, BAT thermogenesis and astrocyte-neuron neurobiology. To this, we use a wide array of methods, such as cell-specific mouse knock-out models, pharmacological treatments, virogenetic manipulation of the central nervous system, complete metabolic phenotyping, indirect calorimetry, immunohistochemical characterization of brain areas, and molecular analyses among others. 

With our research, we are eager to understand the pathophysiology of obesity and its associated comorbidities, contributing thus, to discovering novel pharmacological targets and therapeutic strategies for the treatment of these prevalent metabolic maladies.

Research Lines

  • Hypothalamic nuclear receptors in the regulation of energy balance and obesity.
  • The neuroendocrine role of astrocytes in the hypothalamus.
  • Effects of estrogens on neurocircuits implicated in the control of physiology.

Members

Selected publications

Estradiol regulates leptin sensitivity to control feeding via hypothalamic Cited1.

González-García I, García-Clavé E, Cebrian-Serrano A, et al.

An updated view on human neonatal thermogenesis.

González-García I, Urisarri A, Nogueiras R, Diéguez C, Couce ML & López M

Olfactomedin 2 deficiency protects against diet-induced obesity.

González-García I, Freire-Agulleiro O, Nakaya N, Ortega FJ, Garrido-Gil P, Liñares-Pose L, Fernø J, Labandeira-Garcia JL, Diéguez C, Sultana A, Tomarev SI, Fernández-Real JM & López M

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

Insulin action on astrocytes: From energy homeostasis to behaviour.

González-García I, Tim Gruber, García-Cáceres C.

Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress.

16. González-García I, Contreras C, Estévez-Salguero A, Ruíz-Pino F, Colsh B, Pensado I, Liñares-Pose L, Rial-Pensado E, Martínez de Morentin PB, Fernø J, Diéguez C, Le Stunff H, Magnan C, Nogueiras R, Tena-Sempere M & López M

Selected Results

Figure 1. In our paper from 2023 we discover a new hypothalamic factor, Cited1, and its role in the anorectic effects of both estradiol and leptin (A) Violin plots depict the expression of Agrp, Pomc, Cited1, and Tubb3 genes across the single-cell neuronal clusters. (B) Representative confocal micrographs depicting ERα (yellow) and HA-Tag (magenta) immunoreactivity in the ARC of Cited1-HA mice. (C) Upper panel: Quantification of the relative number of hypothalamic ERα positive neurons which co-express Cited1 in Cited1-HA mice. Lower panel: Quantification of the relative number of hypothalamic Cited1 positive neurons which co-express ERα in Cited1-HA mice. (D and E) Body weight of control or HypΔCited1 male mice fed with chow or HFHS diet. (F and G) Body weight of control or HypΔCited1 female mice fed with chow or HFHS diet. (H) Representative confocal micrographs depicting Cited1 mRNA (red), Pomc mRNA (green) and DAPI (blue) in the ARC of control or PomcΔCited1 mice using RNA scope. (Cell Metabolism | DOI: 10.1016/j.cmet.2023.02.004).

 

Figure 2. In a collaborative project with the Neonatology Service from the University Clinical Hospital of Santiago de Compostela (2021) we studied the brown adipose tissue thermogenesis in the first days after birth. (A) Representative thermal images and (B-D) correlation between body and BAT temperatures in human newborns. (Nature Communications | DOI: 10.1038/s41467-021-25456-z).

 

Figure 3. In our work from 2018, we found that estradiol regulates energy balance by ameliorating hypothalamic ceramide-Induced ER stress. Pharmacological or genetic blockade of ceramide synthesis and amelioration of ER stress selectively occurring in the VMH recapitulate the effect of E2, leading to increased BAT thermogenesis, weight loss, and metabolic improvement. These findings demonstrate that E2 regulation of ceramide-induced hypothalamic lipotoxicity and ER stress is an important determinant of energy balance, suggesting that dysregulation of this mechanism may underlie some changes in energy homeostasis seen in females. (Cell Reports | DOI: doi.org/10.1016/j.celrep.2018.09.038).

Projects

National project(s)

Ayudas para contratos Ramón y Cajal (RYC)
REF: RYC2021-031225-IDuration: -
PI: Ismael González García
AGENCIA ESTATAL DE INVESTIGACION

Alliances

Centro de Investigación Biomédica en Red: Fisiopatología de la Obesidad y Nutrición