A5066282265- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Adipokines, Inflammation, and Metabolic Diseases
- Circadian rhythm and melatonin
- Metabolism, Diabetes, and Cancer
- Sleep and Wakefulness Research
- Cardiovascular Disease and Adiposity
- Endoplasmic Reticulum Stress and Disease
- Growth Hormone and Insulin-like Growth Factors
- Sleep and related disorders
- Diet and metabolism studies
- Nuclear Structure and Function
- Heart Rate Variability and Autonomic Control
- Thyroid Disorders and Treatments
- RNA Research and Splicing
- Dietary Effects on Health
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Hypothalamic control of reproductive hormones
- Cancer, Stress, Anesthesia, and Immune Response
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Toxin Mechanisms and Immunotoxins
- PARP inhibition in cancer therapy
- Cardiac Health and Mental Health
National Institute for Health Research
2024
John Radcliffe Hospital
2024
Oxford Centre for Diabetes, Endocrinology and Metabolism
2022-2024
University of Oxford
2020-2024
Instituto Gulbenkian de Ciência
2017-2023
Universidad Autónoma de Madrid
2021
Instituto de Salud Carlos III
2018-2019
Centro de Investigación Biomédica en Red
2012-2019
Instituto de Investigación Sanitaria de Santiago
2012-2019
Universidade de Santiago de Compostela
2008-2019
Estrogens play a major role in the modulation of energy balance through central and peripheral actions. Here, we demonstrate that action estradiol (E2) inhibits AMP-activated protein kinase (AMPK) estrogen receptor alpha (ERα) selectively ventromedial nucleus hypothalamus (VMH), leading to activation thermogenesis brown adipose tissue (BAT) sympathetic nervous system (SNS) feeding-independent manner. Genetic AMPK VMH prevented E2-induced increase BAT-mediated weight loss. Notably,...
Hypothalamic endoplasmic reticulum (ER) stress is a key mechanism leading to obesity. Here, we demonstrate that ceramides induce lipotoxicity and hypothalamic ER stress, sympathetic inhibition, reduced brown adipose tissue (BAT) thermogenesis, weight gain. Genetic overexpression of the chaperone GRP78/BiP (glucose-regulated protein 78 kDa/binding immunoglobulin protein) in ventromedial nucleus hypothalamus (VMH) abolishes ceramide action by reducing increasing BAT which leads loss improved...
Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis liver and lipid oxidation brown adipose tissue (BAT) through parasympathetic (PSNS) sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic with parallel stimulation of thermogenic program BAT. The action depends on AMP-activated protein kinase (AMPK)-induced regulation two signaling pathways ventromedial nucleus hypothalamus (VMH):...
The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that hypothalamus acts merely as a modulator sympathetic outflow brown adipose tissue (BAT). Recent data have challenged vision by demonstrating THs act ventromedial nucleus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates thermogenic program in BAT, leading increased and weight loss. Current shown addition activation fat, browning white (WAT) might also be an important mechanism....
AMP-activated protein kinase (AMPK) in the ventromedial nucleus of hypothalamus (VMH) and orexin (OX) lateral hypothalamic area (LHA) modulate brown adipose tissue (BAT) thermogenesis. However, whether these two molecular mechanisms act jointly or independently is unclear. Here, we show that thermogenic effect bone morphogenetic 8B (BMP8B) mediated by inhibition AMPK VMH subsequent increase OX signaling via receptor 1 (OX1R). Accordingly, BMP8B totally absent ox-null mice. also induces...
Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation hypothalamic AMPK fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid exhibit up-regulation mammalian target rapamycin (mTOR) signalling pathway mRNA levels agouti-related protein (AgRP)...
Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly with an increased metabolism. An alternative view is that are centrally regulated. We examined here degree which prolonged, infused triiodothyronine (T3) could itself induce total and brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice.Wildtype UPC1 mice were...
The chaperone GRP78/BiP (glucose-regulated protein 78 kDa/binding immunoglobulin protein) modulates folding in reply to cellular insults that lead endoplasmic reticulum (ER) stress. This study investigated the role of hypothalamic GRP78 on energy balance, with particular interest thermogenesis and browning white adipose tissue (WAT). For this purpose, we used diet-induced obese rats administered thapsigargin, by combining metabolic, histologic, physiologic, pharmacologic, thermographic,...
Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns
Significance The age of puberty in humans is changing via unknown mechanisms, although metabolic alterations childhood are blamed as a major contributing factor. Perturbations pubertal timing posed with increased risk later cardiometabolic diseases and reduced life expectancy, urging better understanding the molecular basis for these phenomena. We describe mechanism whereby main cellular energy sensor, AMPK, operates population hypothalamic neurons, named Kiss1, which produce...
AMPK is a cellular gauge that activated under conditions of low energy, increasing energy production and reducing waste. Current evidence links hypothalamic with the central regulation balance. However, it unclear whether targeting has beneficial effects in obesity. Here, we show genetic inhibition ventromedial nucleus hypothalamus (VMH) protects against high-fat diet (HFD)–induced obesity by brown adipose tissue (BAT) thermogenesis subsequently expenditure. Notably, this effect depends upon...
Abstract Increased body weight is a major factor that interferes with smoking cessation. Nicotine, the main bioactive compound in tobacco, has been demonstrated to have an impact on energy balance, since it affects both feeding and expenditure at central level. Among actions of nicotine weight, much attention focused its effect brown adipose tissue (BAT) thermogenesis, though browning white (WAT) unclear. Here, we show induces WAT through mechanism this dependent κ opioid receptor (KOR),...
<h3>Background:</h3> Type 2 familial partial lipodystrophy (FPLD2) is characterised by loss of fat in the limbs and buttocks results from mutations <i>LMNA</i> gene. <h3>Aim:</h3> To evaluate role several genes involved adipogenesis order to better understand underlying mechanisms regional subcutaneous adipose tissue (scAT) patients with FPLD2. <h3>Methods:</h3> In total, 7 FPLD2 10 healthy control participants were studied. A minimal model was used calculate insulin sensitivity (IS). scAT...
Abstract Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation cells. However, (DT) crosses the blood–brain barrier, which limits its utility ablating peripheral cells using Cre drivers that are also expressed in central nervous system (CNS). Here we report development a brain-sparing DT, termed BRAINSPAReDT, genetic outside CNS. We prevent barrier passage DT through PEGylation, polarizes molecule and increases size. validate BRAINSPAReDT with...
3-Iodothyronamine (3-T1AM) is an endogenous thyroid hormone (TH)–derived metabolite that induces severe hypothermia in mice after systemic administration; however, the underlying mechanisms have remained enigmatic. We show here rapid 3-T1AM–induced loss body temperature a consequence of peripheral vasodilation and subsequent heat (e.g., over tail surface). The condition subsequently intensified by hypomotility lack brown adipose tissue activation. Although possible 3-T1AM targets trace...
Summary Background Lipodystrophies are a heterogeneous group of diseases characterized by abnormal fat distribution. Familial partial lipodystrophy 2 (FPLD2) is due to mutations in the LMNA gene. Previous studies have suggested that 5′ nuclear localization signal (NLS) more likely underlie laminopathies with cardiac or skeletal muscle involvement, while 3′ NLS and progeroid syndromes. Objective To study clinical molecular features subject FPLD. Subjects methods We carried out mutational...
Anti-obesity drugs in the amphetamine (AMPH) class act brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite absence of any vivo evidence, is attributed a direct sympathomimetic action heart. Here, we show that cardiac side AMPH originate from can be circumvented PEGylation (PEGyAMPH) exclude its central action. PEGyAMPH does not enter facilitates SNS activity via theβ2-adrenoceptor, protecting mice against...