e-Learning

    In this section you can watch from the comfort of your computer select educational videos or read state of the art articles related to our research interests. In addition, in this section we provide access to important technical manuals and methodologies important to the average biomedical laboratory.

    Online Course 1

    Publication date: November 03, 2015

    Course title: Advances in High Density Lipoprotein Physiology: surprises, overturns and promises

    Course summary: Emerging evidence strongly supports that changes in HDL metabolic pathway that result into changes in HDL proteome and function, appear to have a causative impact on a number of disorders. In a recent paper pubblished in American Journal of Physiology-Endocrinology and Metabolism, we provide a historic review of HDL since its discovery in 1920s focusing on the most recent and novel findings correlating HDL properties and functionality with various pathophysiological processes and disease states, such as obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, inflammation and sepsis, bone and obstructive pulmonary diseases, and brain disorders.

     

    For details please refer to our relevant published work in the American Journal of Physiology-Endocrinology and Metabolism.


    ESF

    The work was financially supported by the action «Excellence» (grant #248, awarded to Prof. Kypreos) of the Operational Program "Education and Lifelong Learning" (Action’s Beneficiary: Hellenic General Secretariat for Research and Technology), that is co-financed by the European Social Fund (ESF) and the Greek State


    Online Course 2

    Publication date: October 01, 2015

    Course title: Deficiency in apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition

    Course summary: Recently, we showed that deficiency in apolipoprotein A-I (ApoA-I) sensitizes mice to diet-induced obesity, glucose intolerance and NAFLD. Here we investigated the potential involvement of ApoA-I in the pharmacological effects of metformin on glucose intolerance and NAFLD development. Groups of apoa1-deficient (apoa1(-/-)) and C57BL/6 mice fed western-type diet were either treated with a daily dose of 300mg/kg metformin for 18 weeks or left untreated for the same period. Then, histological and biochemical analyses were performed. Metformin treatment led to a comparable reduction in plasma insulin levels in both C57BL/6 and apoa1(-/-) mice following intraperitoneal glucose tolerance test. However, only metformin-treated C57BL/6 mice maintained sufficient peripheral insulin sensitivity to effectively clear glucose following the challenge, as indicated by a [(3)H]-2-deoxy-D-glucose uptake assay in isolated soleus muscle. Similarly, deficiency in ApoA-I ablated the effect of metformin on hepatic lipid deposition and NAFLD development. Gene expression analysis indicated that the effects of ApoA-I on metformin treatment may be independent of adenosine monophosphate-activated protein kinase (AMPK) activation and de novo lipogenesis. Interestingly, metformin treatment reduced mitochondrial oxidative phosphorylation function only in apoa1(-/-) mice. Our data show that the role of ApoA-I in diabetes extends to the modulation of the pharmacological actions of metformin, a common drug for the treatment of type 2 diabetes.

    For details please refer to our relevant published work in the European Journal of Pharmacology.



    ESF

    The work was financially supported by the action «Excellence» (grant #248, awarded to Prof. Kypreos) of the Operational Program "Education and Lifelong Learning" (Action’s Beneficiary: Hellenic General Secretariat for Research and Technology), that is co-financed by the European Social Fund (ESF) and the Greek State

    Online Course 3

    Publication date: September 15, 2015

    Course title: HDL beyond atherorpotection: role in obesity and nonalcoholic fatty liver disease

    Course summary: Our recent work highlights the importance of HDL in obesity and nonalcoholic fatty liver disease.
    Briefly, we found that lack of classical ApoA-I containing HDL significantly affected plasma TG metabolism. These mice demonstrated enhanced intestinal absorption of dietary TG, accelerated clearance of postprandial TG, and a reduced rate of hepatic very low density lipoprotein TG production. These mechanistic alterations in plasma TG metabolism correlated with increased diet-induced hepatic TG deposition and disturbed hepatic histology in apoa1-/- mice compared to their wild-type counterparts, while they exhibited reduced glucose tolerance and insulin sensitivity. Interestingly, overexpression of ApoA-IMilano, a gain of function mutant of ApoA-I currently under pharmaceutical development, by adenovirus-mediated gene transfer in apoa1-/-mice led to a significant reduction of hepatic lipid deposition and body weight gain. This observation further reinforced the notion that reduced plasma ApoA-I levels are causative for increased body fat gain and hepatic lipid accumulation.
    Similarly to ApoA-I-deficiency, lack of functional LCAT, thus inhibition of cholesterol esterification in discoidal HDL in plasma, was associated with altered plasma TG metabolism. Lcat-/- mice were also found prone to diet-induced obesity and hepatic lipid deposition, though these mice were resistant to the development of glucose intolerance. Adenovirus-mediated gene transfer of human lcat in lcat-/- mice fed western type diet for 12 weeks resulted in a significant improvement of hepatic lipid deposition combined with body weight loss. Interestingly, LCAT and low-density lipoprotein receptor (LDLR) double deficient mice appear resistant to diet-induced obesity but obviously this reflects a dominant role of LDLR in body-weight gain and white adipose tissue mitochondrial metabolic activation recently seen in mice.
    In a more recent study we also found that SR-BI, the final molecular partner of HDL metabolic pathway in plasma regulates plasma ApoE levels and postprandial TG metabolism in mice. Specifically we found that feeding scarb1-/- mice high fat diet for 24 weeks results in the gradual accumulation of ApoE-containing HDL that ultimately results in insufficient lipoprotein lipase (LpL) activity in circulation. In response, plasma TG levels increase along with the size of TG-rich lipoproteins and subsequent LDLR-mediated clearance of ApoE-containing TG-rich lipoproteins is impaired, despite a compensatory increase in hepatic LDLR expression. Eventually, this leads to inhibition of dietary lipid shuttling to the liver and prevention of diet-induced obesity and NAFLD development. In agreement with these findings in mice, data from bariatric clinical trials reported that rapid weight loss following surgery associated with increased SR-BI-mediated efflux of cholesteryl esters on HDL, leading to increased levels of larger cholesteryl ester-rich HDL2 particles.

    For details please refer to our relevant published work in Molecular Medicine, Journal of Nutritional Biochemistry and Biochemistry.

    The work was financially supported by the action «Excellence» (grant #248, awarded to Prof. Kypreos) of the Operational Program "Education and Lifelong Learning" (Action’s Beneficiary: Hellenic General Secretariat for Research and Technology), that is co-financed by the European Social Fund (ESF) and the Greek State

    Online Course 4

    Publication date: May 26, 2014

    Course title: Revisiting HDL in cardiovascular pharmacology and beyond - HDL apolipoprotein ratios as surrogate markers of HDL functionality and as pharacological targets for HDL based drugs  

    Course summary: In this video we present the highlights of our recent work on the importance of HDL apolipoprotein ratios as markers and as pharmacological targets of HDL -based pharmaceuticals

    For details please refer to our relevant published work in Atherosclerosis and the Journal of Clinical Lipidology 

    Online Course 5

    Publication date: May 17, 2014

    Course title: The LDL receptor is a novel modulator of the effects of testosterone on diet-induced obesity and related metabolic perturbations by affecting WAT metabolic activation. 

    Course summary: In a recent work, we investigated how low density lipoprotein receptor deficiency (Ldlr-/-) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham operated Ldlr-/- mice fed western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and triglyceride profiles, castrated mice were resistant to diet-induced obesity, and had improved glucose metabolism and reduced plasma triglyceride levels, despite a further deterioration in their plasma cholesterol profile. The effect of hypogonadism on diet-induced weight gain of Ldlr-/- mice was independent of ApoE and Lrp1. Indirect calorimetry analysis indicated that hypogonadism in Ldlr-/- mice was associated with increased metabolic rate. Indeed, mitochondrial cytochrome c and Ucp1 expression were elevated, primarily in white adipose tissue, confirming increased mitochondrial metabolic activity due to thermogenesis. Testosterone replacement in castrated Ldlr-/- mice for a period of 8 weeks, promoted diet-induced obesity, indicating a direct role of testosterone in the observed phenotype. Treatment of sham operated Ldlr-/- mice with the aromatase inhibitor exemestane for 8 weeks, showed that the obesity of castrated Ldlr-/- mice is independent of estrogens. Overall, our data reveal a novel role of Ldlr as functional modulator of metabolic alterations associated with hypogonadism.

    For details please refer to our relevant published work in the Journal of Lipid Research

    Online Course 6

    Publication date: May 28, 2013

    Course title: Novel causative relationship between low HDL and diet-induced nonalcoholic fatty liver disease

    Course summary: During the biogenesis of HDL, lipid free or minimally lipidated apoA-I interacts functionally with the lipid transporter ABCA1 to form immature discoidal HDL which are then converted into mature spherical particles by the action of lecithin:cholesterol acyl transferase (LCAT). Here we investigated the mechanistic relationship between low and dysfunctional HDL and diet-induced NAFLD development using mouse models. We employed male apoA-I-deficient (apoA-I-/-) mice that lack classical apoA-I containing HDL and male deficient (LCAT-/-) mice that have immature discoidal HDL. Mice were fed the standard western-type diet for 24 weeks and then histological and biochemical analyses were performed. ApoA-I-/- mice showed increased diet-induced hepatic triglyceride deposition and disturbed hepatic histology while they exhibited reduced glucose tolerance and insulin sensitivity. Quantification of FASN-1, DGAT-1, and PPARγ mRNA expression suggested that the increased hepatic triglyceride content of the apoA-I-/- mice was not due to de novo synthesis of triglycerides. Similarly, metabolic profiling did not reveal differences in the energy expenditure between the two mouse groups. However, apoA-I-/- mice exhibited enhanced intestinal absorption of dietary triglycerides, accelerated clearance of postprandial triglycerides, and a reduced rate of hepatic very low density lipoprotein triglyceride secretion. In agreement with these findings, adenovirus-mediated gene transfer of apoA-IMilano in apoA-I-/- mice fed western-type diet for 12 weeks resulted in a significant reduction in hepatic triglyceride content and an improvement of hepatic histology and architecture. Similar to apoA-I-/- mice, LCAT-/- mice were characterized by increased diet-induced hepatic triglyceride deposition and impaired hepatic histology and architecture. Adenovirus-mediated gene transfer of LCAT in LCAT-/- mice that were fed western-type diet for 12 weeks resulted in a significant reduction in hepatic triglyceride content and a great improvement of hepatic histology and architecture. Taken together, our data establish that the HDL metabolic pathway is a central contributor to the deposition of dietary triglycerides to the liver and the development of NAFLD. Our data further support that the coexistence of reduced HDL levels and NAFLD in an individual with metabolic syndrome may not be a mere coincidence, rather it underlays a strong causative relationship between these two conditions.


    Online Course 7

    Publication date: March 4, 2013

    Course title: HDL particle functionality as a primary pharmacological target for HDL-based therapies

    Course summary: The inverse correlation of plasma HDL-C levels with the slower progression of atherosclerotic lesions seen in numerous epidemiological studies along with a number of atheroprotective properties associated with HDL (including stabilization of unstable atherosclerotic plaques), identified HDL as a beneficial lipoprotein for the prevention of heart disease. Undoubtedly, HDL based therapies have a bright future ahead. However, it is important to redefine their therapeutic target. While the jury is still out on CETP inhibitors, the design of drugs that will simply raise HDL-C levels without improving HDL functionality may have the fate of failed lead compounds of the same class. The primary target of new pharmaceuticals should shift from raising HDL-C levels to improving HDL quality and functionality. Pharmaceuticals that improve HDL atheroprotective functions, enhancing reverse cholesterol transport for example, are expected to exert a significant benefit against CHD related mortality even without increasing HDL-C levels. Of course, more basic research is needed to this effect.  Before we successfully design such pharmaceuticals we need to further explore the exciting world of HDL, deciphering its secret code of atheroprotection. Despite the existing wealth of information we still need to learn more about HDL, and in particular how to harness its properties and exploit its full therapeutic potential for the benefit of the patient.

    For details please Read more


    Online Course 8

    Publication date: January 30, 2013

    Course title: HDL quality in atherosclerosis

    Course summary: Recently the idea that HDL quality is very important for atheroprotection is gaining ground. In particular, particle functionality appears to define whether HDL may be antiatherogenic or even proatherogenic. Our work indicates that measurable changes in HDL apolipoprotein content may serve as effective prognostic markers for the early identification of asymptomatic individuals at high risk for a life-threatening acute myocardial infarction.

    Online Course 9

    Publication date: February 6, 2013

    Course title: HDL in apoCIII-induced hypertriglyceridemia

    Course summary: In this course, I summarize our recent results identiying apoCIII-containing HDL and the lipid transporter ABCA1 as important contributors to the prevention of apoCIII-induced hypertriglyceridemia. Since plasma apoCIII levels correlate with an increased body mass index and the development of insulin resistance, it is possible that apoCIII-containing HDL and the lipid transporter ABCA1 may also be important in the prevention of insulin resistance and type II diabetes.


    Online Course 10

    Publication date: June 16, 2013

    Course title: Instructions for the proper use of Beckman Coulter L-90K preperative ultracentrifuge.

    Course summary: The use of an ultracentrifuge in a laboratory simplifies a number of process that under different conditions would be impossible or very hard to perform. However, we always must keep in mind that an ultracentrifuge is a delicate and potentially dangerous instrument. Improper use may lead to serious damage of the instrument and/or serious injury of the operator. For this reasons, only properly trained personell must be allowed to use it. To assist with the proper use of the instrument, in this course we provide online access to the user manual of the Beckman Coulter L-90K model  and detailed instructions for proper use.

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