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Programa de Medicina Molecular | Obesidad

NeurObesity

Miguel López
Group Leader | Full professor
m.lopez@usc.es
 
Lab: P0L2
Área de conocimiento

The group interest is the field of Obesity, in particular, the hypothalamic regulation of energy balance. The main expertise of the group is hypothalamic neuropeptides (specially orexins), hypothalamic lipid metabolism/AMPK, and ER stress.

You can see the full list of NeuroObesity Group publications in Google Scholar.

Líneas de investigación

  • Hypothalamic AMPK and regulation of whole body energy balance
  • Central actions of thyroid hormones and estrogens
  • Hypothalamic targeting using small extracellular vesicles
  • Human neonatal thermogenesis
  • Central control of catabolic diseases/syndromes, such as rheumatoid arthritis ad cachexia

Miembros

Ánxela María Estévez Salgueiro
Postdoctoral research associate
anxela.estevez@usc.es
Carlos Manuel González Casimiro
Postdoctoral research associate
carlosmanuel.gonzalez@usc.es
Jane Jose Vattathara
Postdoctoral research associate
janejose.vattathara@usc.es

 

Nicolás Fernández Malvido
PhD student
Iara Fernández González
PhD student
Amanda Rodríguez Díaz
FPI fellowship
Óscar Freire Agulleiro
PhD student
Verónica Rivas Limeres
FPI fellowship
Paola Fernández Sanmartín
PhD student

Publicaciones seleccionadas

Obesity wars: hypothalamic sEVs a new hope

Mukherjee S, Diéguez C, Fernø J, López M.

Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice.

Milbank E, Dragano N, Vidal-Gomez X, Rivas-Limeres V, Garrido-Gil P, Wertheimer M, Recoquillon S, Pata MP, Labandeira-Garcia JL, Diéguez C, Nogueiras R, Martínez MC, Andriantsitohaina R & López M

Hypothalamic AMPK as a possible target for energy balance-related diseases

López M.

Activation of hypothalamic AMPK ameliorates metabolic complications of experimental arthritis

Seoane-Collazo P, Rial-Pensado E, Estévez-Salguero A, Milbank E, García-Caballero L, Ríos M, Liñares-Pose L, Scotece M, Gallego R, Fernández-Real JM, Nogueiras R, Diéguez C, Gualillo O & López M

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

Estrogen wars: The activity awakens

López M.

BMP8B sets up brown fat thermogenesis in newborns.

Urisarri A, González-García I, Estévez-Salguero A, Pata MP, Milbank E, López N, Mandiá N, Grijota-Martinez C, Salgado CA, Nogueiras R, Diéguez C, Villarroya F, Fernández-Real JM, Couce ML & López M

Small extracellular vesicle-mediated targeting of hypothalamic AMPKα corrects obesity through BAT activation

Milbank E, Dragano NRV, González-García I, Rios Garcia M, Rivas-Limeres V, Perdomo L, Hilairet G, Ruiz-Pino F, Mallegol P, Morgan DA, Iglesias-Rey R, Contreras C, Vergori L, Cuñarro J, Porteiro B, Gavaldà-Navarro A, Oelkrug R, Vidal A, Roa J, Sobrino T, Villarroya F, Diéguez C, Nogueiras R, García-Cáceres C, Tena-Sempere M, Mittag J, Martínez MC, Rahmouni K, Andriantsitohaina R & López M

Ovarian insufficiency impairs glucose-stimulated insulin secretion through activation of hypothalamic de novo ceramide synthesis.

Meneyrol K, Estévez-Salguero A, González-García I, Guitton J, Taouis M, Benomar Y, Magnan C, López M* & Le Stunff H*

Thyroid wars: the rise of central actions.

Capelli V, Diéguez C, Mittag J & López M

Compounds that modulate AMPK activity and hepatic lipids impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes.

Latorre J, Ortega FJ, Liñares-Pose L, Moreno-Navarrete JM, Lluch A, Comas F, Oliveras-Cañellas N, Ricart W, Höring M, Zhou Y, Liebisch G, Haridas N, Olkkonen VM, López M* & Fernández-Real JM*

Central nicotine induces browning through hypothalamic κ opioid receptor.

Seoane-Collazo P, Liñares-Pose L, Rial-Pensado E, Romero-Picó A, Moreno-Navarrete JM, Martínez-Sánchez N, Garrido-Gil P, Iglesias R, Morgan DA, Tomasini N, Malone S, Senra A, Folgueira C, Medina-Gómez G, Sobrino T, Labandeira-García JL, Nogueiras R, Domingos A, Fernández-Real JM, Rahmouni K, Diéguez C & López M

AMPK Wars: the VMH Strikes Back, Return of the PVH.

López M

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

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

The cellular and molecular bases of leptin and ghrelin resistance in obesity.

Cui H*, López M* & Rahmouni R

A Functional link between ampk and orexin mediates the effect of BMP8B on energy balance.

Martins L, Seoane-Collazo P, Contreras C, González-García I, Martínez-Sánchez N, González F, Zalvide J, Gallego R, Diéguez C, Nogueiras R, Tena-Sempere M & López M

Hypothalamic AMPK: a canonical regulator of whole-body energy balance.

López M, Nogueiras R, Tena-Sempere M & Diéguez C

Estradiol Regulates Brown Adipose Tissue Thermogenesis via Hypothalamic AMPK.

Martínez de Morentin PB, González-García I, Martíns L, Lage R, Fernández-Mallo D, Martínez-Sánchez N, Ruíz-Pino F, Liu J, Morgan D, Pinilla L, Gallego R, Saha AK, Kalsbeek A, Fliers E, Bisschop PH, Diéguez C, Nogueiras R, Rahmouni K, Tena-Sempere M & López M

Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance.

Contreras C, González-García I, Martínez-Sánchez N, Seoane-Collazo P, Jacas J, Morgan DA, Serra D, Gallego R, González F, Casals N, Nogueiras R, Rahmouni K, Diéguez C López M.

BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions.

Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vázquez MJ, Morgan D, Csikasz RI, Gallego R, Rodriguez-Cuenca S, Dale M, Virtue S, Villarroya F, Cannon B, Rahmouni K, López M & Vidal-Puig A

Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.

López M, Varela L, Vázquez MJ, Rodríguez-Cuenca S, González CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R, Martínez de Morentin PB, Tovar S, Nogueiras R, Carling D, Lelliott C, Gallego R, Orešič M, Chatterjee K, Saha AK, Rahmouni K, Diéguez C & Vidal-Puig A

Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin.

López M, Lage R, Saha AK, Pérez-Tilve D, Vázquez MJ, Varela L, Sangiao-Alvarellos S, Tovar S, Raghay K, Rodríguez-Cuenca S, Deoliveira RM, Castañeda T, Datta R, Dong JZ, Culler M, Sleeman MW, Álvarez C, Gallego R, Lelliott CJ, Carling D, Tschöp MH, Diéguez C & Vidal-Puig A

Resultados seleccionados

Central effect of estradiol on AMPK and brown adipose tissue

Although it is well-stablished that estradiol (E2) modulates energy balance, the molecular mechanism mediating those effects are unclear. We have demonstrated that E2 acts through estrogen receptor alpha (ERα) in a precise area of the hypothalamus, the ventromedial nucleus (VMH), to induce thermogenesis in the brown adipose tissue (BAT), leading to increased temperature, energy expenditure and weight loss. Such hypothalamic actions of E2 are mediated via the energy sensor, AMP-activated protein kinase (AMPK) and the sympathetic nervous system (SNS).

Martínez de Morentin PB et al (2014), Cell Metabolism 20:41-53.

 

Central effect of ceramides on hypothalamic ER stress and brown adipose tissue

It is now accepted that the brain senses lipids, such as fatty acids, and modifies energy metabolism accordingly. However, one key question requiring answer was if other lipid species may be involved. We have demonstrated that a particular class of lipids, the ceramides, regulate energy balance through the induction of hypothalamic lipotoxicity and modulation of endoplasmic reticulum functionality (ER stress) in the ventromedial nucleus (VMH). This leads to changes in sympathetic nervous system (SNS) tone and brown adipose tissue (BAT)-induced thermogenesis, impacting on body weight.

Contreras et al (2014), Cell Reports 9:366-377.

 

Central effects of T3 on body lipid metabolism

Thyroid hormones (THs) act in a very precise area of the hypothalamus, named the ventromedial nucleus (VMH), to orchestrate lipid metabolism in liver and brown adipose tissue (BAT). Specifically, triiodothyronine (T3) inhibits AMP-activated protein kinase (AMPK) in the VMH, which lead to changes on one side in ceramides and endoplasmic reticulum (ER) stress and on the other, c-Jun N-terminal kinase (JNK1). Ultimately those effects lead to activation of both the parasympathetic (PSNS) and the sympathetic (SNS) nervous system, which subsequently stimulate lipogenesis in liver and lipid oxidation in BAT. Because of that action, fatty acid and triglyceride (TG) synthesis is activated in liver and liver-derived TGs are taken up by BAT. Here they fuel thermogenesis, which was previously shown to be induced by central T3. The overall effect of these action leads to negative energy balance and weight loss. RPa: raphe pallidus; IO: inferior olive.

Martínez-Sánchez N. et al. (2017), Cell Metabolism 26(1):212-229.

 

Regulation of BAT temperature in human neonates
Representative thermal images of newborns (female upper row and male lower row) at control and cold exposed conditions: basal (0 minutes) and 3, 7 and 11 minutes after cold stimulus. While the body temperature decreases the BAT defends its temperature.

Urisarri A et al (2021) Nature Communications. 12:5274.

Proyectos

National project(s)

Dianas de AMPK hipotalámica y balance energético.
REF: PID2021-128145NB-I00Duration: -
PI: Miguel López Pérez
AGENCIA ESTATAL DE INVESTIGACION
sEVs dirigidas AMPK hipotalámica: una nueva estrategia para el tratamiento de la obesidad y comorbilidades.
REF: PDC2022-133958-I00Duration: -
PI: Miguel López Pérez
AGENCIA ESTATAL DE INVESTIGACION

Alianzas

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

Patentes

Populations of small extracellular vesicles for use in the treatment of obesity
Aplication Nº: EP21382763