APOLIPOPROTEIN E IN DIABETES AND METABOLIC SINDROME
The Metabolic Syndrome (MetS) is a complicated metabolic disorder that increases the risk of developing cardiovascular disease and diabetes, and is closely linked to disturbances in lipid and glucose metabolism. Approximately one-fourth of the adult European population has the MetS and a further increase can be anticipated because of projections of a greater prevalence of obesity in the future. Even Spain, former example of Mediterranean Diet, its prevalence escalates up to 40% in certain subpopulations. Apolipoprotein E (APOE) associates with lipoproteins and mediates their metabolism. In humans, the APOE gene is polymorphic and has three alleles, APOE*2, APOE*3 and APOE*4. Carrying the APOE*4 allele has been associated with an increased cardiovascular risk, predisposition to develop Alzheimer’s disease and insulin resistance. Recently, APOE*4 has also been linked with MetS. However, the mechanisms whereby this association occurs are not clear.
The objective of this project is to investigate the role of APOE in the Metabolic Syndrome by employing a multidisciplinary approach. These disciplines include in vivo analysis of transgenic mouse models as well as biochemical and cell biology experiments, coupled with epidemiological analysis of human populations
PTRF IN ADIPOCYTES
Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is a component of caveolae. It has been demonstrated that PTRF localizes specifically to a caveolae subclass that metabolizes TAG. Moreover, PTRF interacts with HSL in primary human adipocytes and translocates from the plasma membrane to the cytosol in response to insulin treatment, suggesting that PTRF may function in concert with HSL in the regulation of lipolysis These findings point to a potential role of PTRF in regulating lipid metabolism in adipose tissue.
In this project we will assess the functionality of adipocytes in which PTRF has been either overexpressed or knocked-off by lentiviral transduccion.
EFFECTS OF ADIPOCYTE-SECRETED FACTORS ON DECIDUALIZED ENDOMETRIAL CELLS
Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear.
We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this crosstalk for the development of a receptive endometrium. To that end we have generated an in vitro model to investigate the crosstalk between the adipocytes and the endometrial cells. This model has proved valuable to study the effect of estradiol and progesterone on the adipocytes and to evaluate the dynamics of the adipokine receptors and receptivity-related genes in the decidualizing endometrium
EXPANDIBILITY OF THE ADIPOSE TISSUE. BIOMARKERS TO DETERMINE THE LIMIT OF EXPANSION AND THE COMPLICATIONS OF OBESITY.
Obesity is a chronic disease of multifactorial origin defined as an accumulation of fat that causes health
problems. The subcutaneous adipose tissue is able to expand during positive energy balance. However,
expandability is limited and once surpassed there is an ectopic lipid deposition in other organs, which is the
origin of the metabolic disorders associated with obesity.
OBJECTIVES: 1. Study of the biogenesis of subcutaneous adipose tissue, to determine the factors that set the
limit of expansion.2. Develop noninvasive biomarkers that can be used in clinical practice to differentiate obese individuals in which the expansion limit has not yet been reached (benign obesity) of those who have exceeded the limit of expansion and require aggressive therapy.
METHODOLOGY: We included patients from the Department of Surgery who will donate a sample of
subcutaneous fat (prospective study). Abdominal imaging techniques will be performed to determine the level of
adipose tissue expansion, metabolomics in plasma and fat to identify metabolites produced by adipocytes in the
process of expansion and transcriptomics in adipose tissue to determine changes in gene expression related with
the adipogenic process. Biomarkers of interest will be tested in vitro and in a validation cohort. These biomarkers
will decrease the economic and health care burden of obesity on society by allowing an early detection of
pathological obese individuals.