METABOLIC SYNDROME
Exploring the side effects of obesity
My research aims to understand the concepts and mechanisms which underly the complexities of obesity and all the consequences thereof, namely cardiovascular diseases, diabetes, fatty liver, metabolic syndrome.
BIO
Who I Am
I’m a professional Biomedical Researcher living in Israel, exploring and researching the processes and scientific mechanisms underlying our modern world we live in. I am especially interested in metabolic diseases; Diabetes, Cardiovascular Diseases, Metabolic Syndrome and Fatty Liver Disease and how our western life style contributes to the development of these ailments.
MY RESEARCH
Unlocking Metabolic Syndrome
The metabolic syndrome is a medical disorder defined by the World Health Organization (WHO) with: impaired glucose tolerance, impaired fasting glucose or insulin resistance, and at least two of the following: high blood pressure, dyslipidemia (hypertriglyceridaemia), central obesity (excess body fat around the waist) or microalbuminuria. These conditions culminate in the risk of developing diabetes mellitus type 2, cardiovascular disease (atherosclerosis) leading to heart failure or stroke, the latter being the leading cause of death in industrialized countries.
The urokinase-type plasminogen activator and its receptor system (uPA/uPAR) has emerged as a proinflammatory marker under pathogenic conditions such as obesity, kidney disease, type I diabetes, cardiovascular diseases, as well as as a predictor of cancer, cardiovascular disease, diabetes and mortality in general healthy populations.
PROGRESSION OF THE ATHEROSCLEROTIC LESION
2013
In an effort to gain a better understanding of the development of an atherosclerotic lesion, one of my projects focused on the urokinase-type plasminogen activator/urokinase-type plasminogen activtor receptor (uPA/uPAR) system, which showed to be important for the development of atherosclerosis; in particular I investigated on monocyte-macrophage conversion, one of the major hallmarks of atherosclerosis [9]. Using mice deficient of the uPA receptor (uPAR-/-) and the macrophage-like cell line MM6, I discovered that uPA intensified PMA-induced differentiation of THP-1 monocytes to macrophages by driving the MM6 cells into G1 arrest. Further, macrophage apoptosis induced by oxidized LDL was attenuated by uPA through down regulation of the proapoptotic protein Bim. These processes might result in increased numbers of macrophages in the lesion and prolonged macrophage survival which accelerates lesion development and contributes to the worsening of atherosclerosis [10].
NON-ALCOHOLIC FATTY LIVER DISEASE
2014
Cardiovascular disease is the major cause of death in patients with non-alcoholic fatty liver disease (NAFLD) affecting 10% - 24% of the population worldwide, and is considered to be the hepatic manifestation of the metabolic syndrome. It is characterized by the presence of triglyceride droplets in more than 5% of hepatocytes by consumption of >Â 20 g alcohol/day. Treating the hepatocyte cell line Huh7 with uPA in increasing concentrations led to upregulation of triglyerides concentration dependently. This was connected to the enhancement of de novo synthesis of triglycerides and to the blockage of the release of triglyceride-carrying vesicles through the action of Diglyceride acyltransferase 2 (DGAT2). Moreover, uPAR-/- mice were protected from accumulation of lipid droplets in the liver showing the importance of this mechanism also in vivo.
FUTURE PROJECTS
2019
Investigation of (i) the role of the uPA/uPAR system for the proinflammatory processes in the microenvironment and (ii) intra- and intercellular signalling pathways involved in the development of the metabolic syndrome with a focus on NAFLD and Diabetes in obesity. Meta-inflammation caused by obesity is known to be similar to inflammation caused by pathogens, showing characteristics such as increase of circulating inflammatory cytokines and acute phase proteins (e.g. C-reactive protein), and activation of tissue leucocytes. Meta-inflammation became widely accepted as a link between obesity and metabolic diseases
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