Papel del tejido adiposo blanco, marrón y perivascular en las complicaciones vasculares asociadas a la obesidad

Obesity is a worldwide epidemics. It represents a public health alarm associated to several metabolic diseases such as type 2 diabetes, dyslipidemia, systolic hypertension, fatty liver, gastrointestinal cancer and neurodegenerative diseases as Alzheimer disease. Some of them involve high cardiovascular disease risk and damage. The adipose organ it is composed by two different kinds of adipose tissues differing in morphology, distribution, genes and function. The white adipose tissue is mainly involved in lipid storage while the brown adipose tissue participates in the adaptive thermogenesis. Both of them secrete specific adipokines such as leptin, adiponectin or resistin and also adipocytokynes such as TNFα or Interleukins 6 and 1β that trigger a local inflammatory process associated with a primary insulin resistance in the adipose tissues and a vascular effect through prothrombogenic molecules such as Angiotensin II or PAI-I. The activation of the brown adipose tissue confers an obesity resistance. Conversely, the loss of functional brown adipose tissue confers an obesity prone in mice and humans.La obesidad es en la actualidad una epidemia mundial. La obesidad se ha convertido en un problema de salud pública no sólo por el aumento de la estigmatización social, el problema económico que supone o el fallo en la calidad de vida, sino también por el riesgo asociado que presentan dichos pacientes a desarrollar otras patologías como la diabetes tipo 2, dislipidemias, hígado graso, aterosclerosis, enfermedad cardiovascular, enfermedad de Alzheimer, enfermedades óseas y con frecuencia algunos tipos de cánceres especialmente digestivos, algunas de las cuales conllevan un riesgo cardiovascular elevado. En mamíferos el tejido adiposo está compuesto al menos por dos tipos muy distintas de grasas como son el tejido adiposo blanco (TAB) y el tejido adiposo marrón o pardo (TAM) que presentan diferencias en cuanto a su morfología, distribución, genes y función. El tejido adiposo blanco es el principal reservorio de energía y libera un gran número de hormonas y citoquinas que modulan el metabolismo del organismo y la resistencia a la insulina. Algunas de estas moléculas están implicadas en la regulación del peso corporal (leptina, adiponectina), en la respuesta inflamatoria generada localmente en una situación de obesidad (TNF-α, interlukina-6 e IL-1β), en la función vascular (Angiotensina II y PAI-1) o reproductora (estrógenos, entre otras). El tejido adiposo marrón está formado por adipocitos marrones y células progenitoras de adipocitos. La activación del tejido adiposo marrón reduce la adiposidad y protege frente a la obesidad. Por el contrario, la pérdida de la masa del tejido adiposo marrón, confiere susceptibilidad a desarrollar obesidad en ratones y en humanos

Papel de la isoforma A del receptor de la insulina y del IGF-1R en el crecimiento de la placa aterosclerótica

In this work, we have obtained new lines of vascular smooth muscle cells (VSMCs) to demonstrate that IRA and IRA/IGF-1R might confer a proliferative and migratory advantage in response to insulin, IGF-2 or TNF-α. These results might be relevant due to in the early stages of atherosclerotic process; we have demonstrated that there is a significant increase of IRA and IGF-1R expression as well as higher formation of hybrid receptors in the aorta from two models of early atherosclerosis. Finally, anti-TNF-α treatment prevented vascular alterations.En este trabajo se han obtenido nuevas líneas de células de músculo liso vascular (VSMCs) que nos han permitido demostrar que la IRA e IRA/IGF-1R podrían conferirles una ventaja proliferativa y migratoria en respuesta a insulina, IGF-2 o TNF-α. Estos resultados podrían ser relevantes ya que en las fases iniciales del proceso aterogénico nosotros hemos demostrado que hay un aumento significativo de la expresión de la IRA e IGF-1R así como una mayor presencia de receptores híbridos en la aorta de dos modelos experimentales de aterosclerosis temprana. Y finalmente, como el tratamiento con un anticuerpo anti-TNF-α previno las alteraciones vasculares

Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue

The aim of the present work was to study the consequences of chronic exercise training on factors involved in the regulation of mitochondrial remodeling and biogenesis, as well as the ability to produce energy and improve insulin sensitivity and glucose uptake in rat brown adipose tissue (BAT). Male Wistar rats were divided into two groups: (1) control group (C; n = 10) and (2) exercise-trained rats (ET; n = 10) for 8 weeks on a motor treadmill (five times per week for 50 min). Exercise training reduced body weight, plasma insulin, and oxidized LDL concentrations. Protein expression of ATP-independent metalloprotease (OMA1), short optic atrophy 1 (S-OPA1), and dynamin-related protein 1 (DRP1) in BAT increased in trained rats, and long optic atrophy 1 (L-OPA1) and mitofusin 1 (MFN1) expression decreased. BAT expression of nuclear respiratory factor type 1 (NRF1) and mitochondrial transcription factor A (TFAM), the main factors involved in mitochondrial biogenesis, was higher in trained rats compared to controls. Exercise training increased protein expression of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and AMP-activated protein kinase (pAMPK/AMPK ratio) in BAT. In addition, training increased carnitine palmitoyltransferase II (CPT II), mitochondrial F1 ATP synthase α-chain, mitochondrial malate dehydrogenase 2 (mMDH) and uncoupling protein (UCP) 1,2,3 expression in BAT. Moreover, exercise increased insulin receptor (IR) ratio (IRA/IRB ratio), IRA-insulin-like growth factor 1 receptor (IGF-1R) hybrids and p42/44 activation, and decreased IGF-1R expression and IR substrate 1 (p-IRS-1) (S307) indicating higher insulin sensitivity and favoring glucose uptake in BAT in response to chronic exercise training. In summary, the present study indicates that chronic exercise is able to improve the energetic profile of BAT in terms of increased mitochondrial function and insulin sensitivity

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain

Background: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. Methods: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). Results: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95% CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. Conclusions: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain

Human amylin aggregates release within exosomes as a protective mechanism in pancreatic β cells: Pancreatic β-hippocampal cell communication

Pancreatic β cells are essential in the maintenance of glucose homeostasis during the progression to type 2 Diabetes Mellitus (T2DM), generating compensatory hyperinsulinemia to counteract insulin resistance. It is well known, that throughout the process there is an increased mTORC1 signaling pathway, with an impairment in different quality control systems including ubiquitin-proteasome system and autophagy. In addition, under this situation, pancreatic β cells start to accumulate amylin protein (IAPP) in aggregates, and this accumulation contributes to the failure of autophagy, damaging different organelles such as plasma membrane, endoplasmic reticulum, mitochondria, and others. Here, we report that IAPP can be incorporated to multivesicular bodies (MVB) and secreted into exosomes, a mechanism responsible for the exportation of these toxic aggregates as vehicles of cell to cell communication. On this regard, we have demonstrated that the exosomes bearing toxic hIAPP released from pancreatic β cells are capable to induce hyperactivation of mTORC1 signaling, a failure in the autophagic cellular quality control, and favor pro-fission status of the mitochondrial dynamics in hippo-campal cells. In summary, our results show that harmful accumulation of hIAPP in pancreatic β cells may be detoxified by the release of exosomes, which may be captured by endocytosis mechanism damaging neuronal hippocampal cells, which suggest an underlying molecular mechanism to the link between type 2 diabetes and neurodegenerative diseases

Prevalence of dementia and major dementia subtypes in Spanish populations: A reanalysis of dementia prevalence surveys, 1990-2008

Background This study describes the prevalence of dementia and major dementia subtypes in Spanish elderly. Methods We identified screening surveys, both published and unpublished, in Spanish populations, which fulfilled specific quality criteria and targeted prevalence of dementia in populations aged 70 years and above. Surveys covering 13 geographically different populations were selected (prevalence period: 1990-2008). Authors of original surveys provided methodological details of their studies through a systematic questionnaire and also raw age-specific data. Prevalence data were compared using direct adjustment and logistic regression. Results The reanalyzed study population (aged 70 year and above) was composed of Central and North-Eastern Spanish sub-populations obtained from 9 surveys and totaled 12,232 persons and 1,194 cases of dementia (707 of Alzheimer's disease, 238 of vascular dementia). Results showed high variation in age- and sex-specific prevalence across studies. The reanalyzed prevalence of dementia was significantly higher in women; increased with age, particularly for Alzheimer's disease; and displayed a significant geographical variation among men. Prevalence was lowest in surveys reporting participation below 85%, studies referred to urban-mixed populations and populations diagnosed by psychiatrists. Conclusion Prevalence of dementia and Alzheimer's disease in Central and North-Eastern Spain is higher in females, increases with age, and displays considerable geographic variation that may be method-related. People suffering from dementia and Alzheimer's disease in Spain may approach 600,000 and 400,000 respectively. However, existing studies may not be completely appropriate to infer prevalence of dementia and its subtypes in Spain until surveys in Southern Spain are conductedFinancial aid was obtained from the Spanish RECSP C03-09, CIEN C03-06 and CIBERNED networks, and from the Pfizer Foundation in particularS