Grupo-Otra-Actividad-GIIS065

PROYECTOS ACTIVOS

LIPOPROTEIN PROFILING 4 HCV INFECTION

Hepatitis C Virus (HCV) associates with lipoproteins being secreted from the liver as highly infective lipoviro particles (LVP). These LVP markedly interfere with the host lipid metabolism, ultimately causing a wide array of extrahepatic manifestations of chronic infection such as liver steatosis and cardiovascular disease (CVD). Characterizing this impaired lipid homeostasis is hence of vital importance. Yet, previous research investigating the interaction of HCV genotypes and direct-acting antiviral (DAA) treatments on lipid metabolism leaves some aspects not yet addressed. We hypothesize that measuring the number and size of lipoprotein subclasses will provide a better tool to address HCV-mediated lipid remodeling rather than the classical measures of lipoprotein-borne cholesterol. Additionally, APOE is a structural component of HCV-LVP and plays important roles in HCV infection and virion assembly. However, previous epidemiological studies have also showed conflicting results regarding the differential role of APOE isoforms on circulating lipoproteins after DAA treatments. We hypothesize that those discrepant results may result as not-yet known interactions between APOE genotypes and HCV genotypes and their modulation by HCV treatments.
The aim of this study will be 1) to clinically and epidemiologically characterize the dyslipidemia caused by the HCV as well as the persistence of the altered lipid profile after the most common DAA treatments with the application of the DOSY method to calculate lipoprotein number and size, and 2) evaluate how polymorphisms in the APOE are associated with the HCV- and DAA- mediated lipid remodeling, accounting for HCV genotypes and different DAA treatments as confounding factors.

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.