NeurObesity
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.
Research Lines
- 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
Members
Selected publications
Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice.
Hypothalamic AMPK as a possible target for energy balance-related diseases
Activation of hypothalamic AMPK ameliorates metabolic complications of experimental arthritis
Small extracellular vesicle-mediated targeting of hypothalamic AMPKα corrects obesity through BAT activation
Ovarian insufficiency impairs glucose-stimulated insulin secretion through activation of hypothalamic de novo ceramide synthesis.
Compounds that modulate AMPK activity and hepatic lipids impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes.
Central nicotine induces browning through hypothalamic κ opioid receptor.
AMPK Wars: the VMH Strikes Back, Return of the PVH.
Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress.
Hypothalamic AMPK-ER stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance
The cellular and molecular bases of leptin and ghrelin resistance in obesity.
A Functional link between ampk and orexin mediates the effect of BMP8B on energy balance.
Hypothalamic AMPK: a canonical regulator of whole-body energy balance.
Estradiol Regulates Brown Adipose Tissue Thermogenesis via Hypothalamic AMPK.
Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance.
BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions.
Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.
Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin.
Selected Results
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.
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