Diabetes y obesidad con el envejecimiento (DOE)
Área de tecnología para la salud, medicina de precisión y envejecimiento
In this setting, the laboratory “Diabetes y Obesidad con el Envejecimiento (DOE)” aims to understand the molecular and cellular mechanisms of insulin and leptin resistance associated with aging. This integrative project includes the study in vivo and in vitro of all the main insulin target tissues and the interrelationships between insulin and leptin signaling on glucose and lipid metabolism.
In this sense, one aim of our laboratory is to understand how a diminished/deficient central leptin signaling in young leptin sensitive rats is associated to hypothalamic nuclei-specific alterations leading to modifications in eating behavior, locomotor activity and whole-body insulin sensitivity, mimicking the metabolic characteristic of aged rats. We also study whether the central leptin deficiency is associated to hypothalamic nuclei-specific changes in the protein/lipid profile composition by means of mass spectrometry analysis, microglia activation/proliferation and inflammation.
We are also interested to understand whether alterations in the plasma membrane lipid composition of visceral adipose tissue in aged rats, which favors an enlarged fat cell size, could constitute a possible survival mechanism preventing that the aged rats from becoming overtly diabetic. Because the hypothalamic-adipose tissue axis is highly related with adiposity and inflammatory disorders, another goal of our research is to investigate whether the central leptin signaling deficiency alters the visceral adipose tissue plasma membrane lipid composition and the sphingolipid metabolism, as well as the local inflammatory response.
Another goal of our research is to elucidate the precise underling mechanisms by which central leptin, at very low doses, regulates cardiac metabolism and protects against cardiac hypertrophy by regulating PPARs transcription factors. To this end, we study cardiac oxidative and thermogenic capacity, mitochondrial and peroxisomal biogenesis and dynamics as well as functional alterations of proteins from ventricles by means of proteomics technique. This project will contribute to highlight the cellular events involved in the cardioprotective effects of leptin.
The adipokine leptin regulates food intake and peripheral glucose and lipid metabolism through the central melanocortin system and the autonomic nervous system. Hence, we are interested in study how a diminished/deficient central leptin signaling, which promotes ectopic fat deposition in peripheral tissues, impact the physiological function of the endocrine pancreas altering the circulating insulin and glucagon levels. Thus, one aim of our laboratory is to understand the role of the hypothalamic-liver-pancreas axis on the regulation of insulin and glucagon levels mediated by central leptin signaling.
- ANTONIO ANDRÉS HUEVA
- NILDA GALLARDO ALPÍZAR
- MARGARITA VILLAR RAYO
- CARMEN ARRIBAS MOCOROA
- EDUARDO MOLTÓ PÉREZ
- CRISTINA PINTADO LOSA
- MARÍA RODRÍGUEZ PÉREZ
- ELENA BONZÓN-KULICHENCO
- LORENA MAZUECOS FERNÁNDEZ-PACHECO
- SARA ARTIGAS JERÓNIMO
- BLANCA RUBIO