In this thesis, we have addressed two key objectives: 1) to gain more insight in various pathophysiological aspects of cardiometabolic diseases including in the disease proneSouth Asian population,... Show moreIn this thesis, we have addressed two key objectives: 1) to gain more insight in various pathophysiological aspects of cardiometabolic diseases including in the disease proneSouth Asian population, and 2) to study the physiological effects of cold exposure and identify a novel pharmacological approach to directly target BAT. Show less
Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. In 2018, the ACS EuroPath... Show morePost-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. In 2018, the ACS EuroPath Survey, performed in collaboration with 555 European cardiologists, identified a sub-optimal LDL-C management in post-ACS patients.Based on these premises, the ACS EuroPath II project led to the development of a self-assessment tool to improve lipid management in these very high risk patients, taking into consideration the new 2019 ESC/EAS guidelines. This tool is built in 3 sections. The first is a questionnaire to assess the lipid management practice from the acute phase up to 12 months of follow-up. The main topics covered in this section relate to 1) acute phase (lipid management of ACS patients during hospitalization; 2) discharge (lipid management at discharge, with focus on follow-up plan); 3) follow-up (lipid management at the time of first and subsequent follow-ups); 4) referral pathway for definitive lipid management care of post-ACS patients; 5) evaluation of the achieved goal at 6 months to 1 year and key implications. The second section is a brief report to position the results against other European Union clinical practice and European guidelines. The last section allows the physician to evaluate and consider the implementation of one or more strategies, successfully developed in leading European centers, in order to optimize their own clinical practice.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
This review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoim...Show moreThis review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoimmunity. Multiple therapeutic approaches using existing pharmaceuticals are possible from a rationale in which T cell metabolism forms the hub in dampening the T cell component of autoimmunity in metabolic diseases. Future research into the effects of a metabolically aberrant micro-environment on T cell metabolism and its potential as a therapeutic target for immunomodulation could lead to novel treatment strategies for metabolic disease-associated autoimmunity. Show less
Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease, and its worldwide prevalence continues to increase in parallel of the obesity epidemic.... Show moreNon-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease, and its worldwide prevalence continues to increase in parallel of the obesity epidemic. NAFLD comprises a wide spectrum of liver damage ranging fat accumulation (steatosis) to steatosis with inflammation (non-alcoholic steatohepatitis, NASH), which can further progress to fibrosis. In particular patients with NASH have increased risk to develop other metabolic complications, such as cardiovascular disease.NAFLD is a complex disease, in which the origin and molecular mechanisms controlling the progression of simple steatosis to NASH remain poorly understood. Nevertheless, it is thought that inflammation is a critical component of NAFLD progression. This inflammation may be triggered by metabolic surplus (excess of energy or nutrients) and is also referred to as “metabolic inflammation”. White adipose tissue (WAT) is assumed to be largely involved in the development of metabolic inflammation. The studies described in this thesis contributed to the understanding of the role of WAT in the development of NAFLD and provide insight into the molecular processes that cause metabolic inflammation. Show less
This review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and... Show moreThis review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoimmunity. Multiple therapeutic approaches using existing pharmaceuticals are possible from a rationale in which T cell metabolism forms the hub in dampening the T cell component of autoimmunity in metabolic diseases. Future research into the effects of a metabolically aberrant micro-environment on T cell metabolism and its potential as a therapeutic target for immunomodulation could lead to novel treatment strategies for metabolic disease-associated autoimmunity. Show less
This review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and... Show moreThis review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoimmunity. Multiple therapeutic approaches using existing pharmaceuticals are possible from a rationale in which T cell metabolism forms the hub in dampening the T cell component of autoimmunity in metabolic diseases. Future research into the effects of a metabolically aberrant micro-environment on T cell metabolism and its potential as a therapeutic target for immunomodulation could lead to novel treatment strategies for metabolic disease-associated autoimmunity. Show less
This review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and... Show moreThis review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoimmunity. Multiple therapeutic approaches using existing pharmaceuticals are possible from a rationale in which T cell metabolism forms the hub in dampening the T cell component of autoimmunity in metabolic diseases. Future research into the effects of a metabolically aberrant micro-environment on T cell metabolism and its potential as a therapeutic target for immunomodulation could lead to novel treatment strategies for metabolic disease-associated autoimmunity. Show less
This review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and... Show moreThis review discusses the relevant metabolic pathways and their regulators which show potential for T cell metabolism-based immunotherapy in diseases hallmarked by both metabolic disease and autoimmunity. Multiple therapeutic approaches using existing pharmaceuticals are possible from a rationale in which T cell metabolism forms the hub in dampening the T cell component of autoimmunity in metabolic diseases. Future research into the effects of a metabolically aberrant micro-environment on T cell metabolism and its potential as a therapeutic target for immunomodulation could lead to novel treatment strategies for metabolic disease-associated autoimmunity. Show less
Overload of nutrients can lead to diet-induced inflammation, also called metabolic inflammation, which is thought to play an important role in many metabolic diseases, including the development of... Show moreOverload of nutrients can lead to diet-induced inflammation, also called metabolic inflammation, which is thought to play an important role in many metabolic diseases, including the development of nonalcoholic fatty liver disease (NAFLD). NAFLD encompasses a spectrum of pathologies that range from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis. The pathogenesis of NAFLD, including the sequence of events in time and the underlying mechanisms that initiate the transition from a fatty liver to NASH and fibrosis, remain poorly understood. Effective and reliable therapeutic approaches that are based on the understanding of the pathogenesis of NASH are therefore still lacking. In order to gain more insight into the mechanisms of NASH pathogenesis, we started with comparison of human NASH and experimental NASH. Subsequently, we provided evidence that activation of AP-1 and associated neutrophil infiltration is important for NAFL progression towards NASH and this can be induced experimentally by __metabolic__ dietary triggers of inflammation.Furthermore, we explored novel nutritional and pharmacological agents as potential strategies to combat NASH. Finally, we investigated the effects of high fat diet-induced metabolic overload on the liver in relation to inflammation in white adipose tissue and kidney, and the dysfunction of these tissues. Show less
The aim of this thesis was to clarify which aspects of depression and anxiety are related to an increased metabolic risk, and which factors contribute to these associations. Taken together, our... Show moreThe aim of this thesis was to clarify which aspects of depression and anxiety are related to an increased metabolic risk, and which factors contribute to these associations. Taken together, our findings indicate that people with more severe symptoms of depression and anxiety are at particular risk of progressive dyslipidemia and (abdominal) obesity. The higher rates of smoking and systemic inflammation among people with depression or anxiety partially accounted for their adverse metabolic profile. Dysregulations of the autonomic nervous system partly explained why users of tricyclic antidepressants displayed an increased risk of dyslipidemia and (abdominal) obesity as well, and also of hypertension. These important findings shed light on useful avenues for future research, and on preventive and therapeutic insights and directions. Show less
