Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults,but also in adolescents.The metabolic syndrome,a complex cluster of metabolic abnormalities,increases one’s risk of developing...Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults,but also in adolescents.The metabolic syndrome,a complex cluster of metabolic abnormalities,increases one’s risk of developing type 2 diabetes and cardiovascular disease(CVD).Dyslipidemia,a key component of the metabolic syndrome,is highly associated with insulin resistance and contributes to increased CVD risk.Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e.fasting triglycerides,total cholesterol,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)].However,the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk.In insulin resistant states,the intestine overproduces triglyceride-rich lipoprotein(TRL) particles,termed chylomicrons(CMs),following ingestion of a fat-containing meal,as well as in the fasting state.Along with elevated hepatic TRLs(i.e.very-low density lipoproteins),CMs contribute to remnant lipoprotein accumulation,small dense LDL particles,and reduced HDL-C,which collectively increase CVD risk.Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence,studying postprandial dyslipidemia in the adolescent population is an important area of study.Postprandial dyslipidemia in the pediatric population poses a significant public health concern,warranting a better understanding of its pathogenesis and association with insulin resistance and CVD.This review discusses the metabolic syndrome,focusing on the link between insulin resistance,postprandial dyslipidemia,and CVD risk.Furthermore,the clinical significance and functional assessment of postprandial dyslipidemia,specifically in the adolescent population,is discussed in more detail.展开更多
Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mel...Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus.Several reasons exist for peripheral arterial disease indiabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally,the use of certain specific postprandial particle markers,such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles.展开更多
Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulat...Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulators of this pathway. Autophagy is a degradative process that targets cellular components to the lysosome and recent studies have indicated a role for autophagy in regulating hepatic lipid metabolism(known as lipophagy) as well as lipoprotein assembly. Autophagy directly targets apolipoprotein B-100(apoB100), the structural protein component of very lowdensity lipoproteins(VLDLs), and further targets lipid droplets(LDs), the cellular storage for neutral lipids.Autophagy thus plays a complex and dual role in VLDL particle assembly by regulating apoB 100 degradation as well as aiding the maturation of VLDL particles by hydrolyzing lipid from LDs. The purpose of this article is to review our current understanding of molecular and cellular mechanisms mediating authophagic control of hepatic lipid biogenesis and VLDL production as well as dysregulation in insulin resistance and dyslipidemia.展开更多
The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that aff...The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.展开更多
文摘Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults,but also in adolescents.The metabolic syndrome,a complex cluster of metabolic abnormalities,increases one’s risk of developing type 2 diabetes and cardiovascular disease(CVD).Dyslipidemia,a key component of the metabolic syndrome,is highly associated with insulin resistance and contributes to increased CVD risk.Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e.fasting triglycerides,total cholesterol,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)].However,the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk.In insulin resistant states,the intestine overproduces triglyceride-rich lipoprotein(TRL) particles,termed chylomicrons(CMs),following ingestion of a fat-containing meal,as well as in the fasting state.Along with elevated hepatic TRLs(i.e.very-low density lipoproteins),CMs contribute to remnant lipoprotein accumulation,small dense LDL particles,and reduced HDL-C,which collectively increase CVD risk.Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence,studying postprandial dyslipidemia in the adolescent population is an important area of study.Postprandial dyslipidemia in the pediatric population poses a significant public health concern,warranting a better understanding of its pathogenesis and association with insulin resistance and CVD.This review discusses the metabolic syndrome,focusing on the link between insulin resistance,postprandial dyslipidemia,and CVD risk.Furthermore,the clinical significance and functional assessment of postprandial dyslipidemia,specifically in the adolescent population,is discussed in more detail.
基金Supported by Grant to Grupo CTS-159 of PAIDI(Plan Andaluz de Investigación,Desarrollo e Innovación) de la Junta de Andalucía
文摘Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus.Several reasons exist for peripheral arterial disease indiabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally,the use of certain specific postprandial particle markers,such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles.
文摘Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulators of this pathway. Autophagy is a degradative process that targets cellular components to the lysosome and recent studies have indicated a role for autophagy in regulating hepatic lipid metabolism(known as lipophagy) as well as lipoprotein assembly. Autophagy directly targets apolipoprotein B-100(apoB100), the structural protein component of very lowdensity lipoproteins(VLDLs), and further targets lipid droplets(LDs), the cellular storage for neutral lipids.Autophagy thus plays a complex and dual role in VLDL particle assembly by regulating apoB 100 degradation as well as aiding the maturation of VLDL particles by hydrolyzing lipid from LDs. The purpose of this article is to review our current understanding of molecular and cellular mechanisms mediating authophagic control of hepatic lipid biogenesis and VLDL production as well as dysregulation in insulin resistance and dyslipidemia.
文摘The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.
