Clinical Lipidology

AIM: The aim of this study was to test small dense LDL changes with Armolipid Plus treatment in patients with familial combined hyperlipidemia (FCHL). METHODS: After 4 weeks, 30 patients with FCHL were included in an 8-week, randomized, double-blind study and were taking, in addition to the standard diet, either placebo or Armolipid Plus. RESULTS: The placebo group showed no statistically significant differences in the studied parameters; instead, in the Armolipid Plus group, statistically significant reduction differences were detected in BMI (p = 0...

Lipoprotein X (LpX) is an abnormal lipoprotein found in conditions such as lecithin:cholesterol acyltransferase deficiency and cholestatic states (e.g., primary biliary cirrhosis and primary sclerosing cholangitis). Management of severe hypercholesterolemia due to LpX with drugs and physical removal methods is not well established in the literature. A case is discussed of a 51-year-old woman who presented with multiple electrolyte abnormalities, xanthomas and neuropathy found to be secondary to LpX in the setting of primary sclerosing cholangitis...

No abstract text is available yet for this article.

Testosterone prescriptions have risen steadily and sharply in the USA despite a lack of clear understanding of the relationship between androgens and cardiovascular disease. In men with increasing age, testosterone levels decline and cardiovascular disease risk goes up. Ties between hypogonadism and cardiovascular disease are suggested by observational data, yet therapy with testosterone replacement has not been shown to mitigate that risk. To the contrary, recent literature has raised concern for increased cardiovascular disease in certain groups of men receiving testosterone therapy...

Elevated post-prandial lipoprotein levels are common in patients with type 2 diabetes. Post-prandial lipoprotein alterations in type 2 diabetics are widely believed to drive inflammation and are considered a major risk factor for cardiovascular disease in diabetic patients. The incretins glucagon like peptide-1 (GLP-1) and glucose insulinotropic peptide (GIP) modulate post-prandial lipoproteins through a multitude of pathways that are independent of insulin and weight loss. Evidence from both animal models and humans seems to suggest an important effect on triglyceride rich lipoproteins (Apo48 containing) with little to no effects on other lipoproteins at least in humans...

Despite wide use of statins, significant cardiovascular disease risk persists. High-density lipoprotein based therapy has not yielded any positive results in combating this disease. Newer methods to rapidly decrease plasma cholesterol are much needed. While apolipoprotein B is a ligand for low-density lipoprotein receptor, which clears low-density lipoprotein cholesterol in a highly regulated pathway, apolipoprotein E (apoE) is a ligand for clearing other apolipoprotein B containing atherogenic lipoproteins via an alternate receptor pathway, especially the heparin sulfate proteoglycans on the liver cell surface...

The development of therapies for neuropsychiatric disorders is hampered by the lack of understanding of the mechanisms underlying their pathologies. While aberrant sphingolipid metabolism is associated with psychiatric illness, the role of sphingolipids in these disorders is not understood. The genetically tractable yeast model can be exploited in order to elucidate the cellular consequences of sphingolipid perturbation. Hypotheses generated from studies in yeast and tested in mammalian cells may contribute to our understanding of the role of sphingolipids in psychiatric disorders and to the development of new treatments...

Climbing obesity rates have contributed to worldwide increases in obesity-associated diseases, including the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Sphingolipids, an important class of structural and signaling lipids, have emerged as key players in the development and pathogenesis of insulin resistance and T2DM. More specifically, sphingolipids have been demonstrated to play integral roles in lipotoxicity and other aspects of pathogenesis in T2DM, although the cellular mechanisms by which this occurs and by which sphingolipid metabolism is dysregulated in T2DM remain under investigation...

No abstract text is available yet for this article.

Atherosclerosis is a chronic inflammation in the arterial wall involving cells of the innate and adaptive immune system that is promoted by hyperlipidemia. In addition, the immune system can influence lipids and lipoprotein levels and cellular lipid homeostasis can influence the level and function of the immune cells. We will review the effects of manipulation of adaptive immune cells and immune cell products on lipids and lipoproteins, focusing mainly on studies performed in murine models of atherosclerosis...

Oxysterols are metabolites of cholesterol that are produced in liver and other peripheral tissues as a means to eliminate cholesterol to bile acid. Recent studies have revealed that the most abundant circulating oxysterol 27-hydroxycholesterol (27HC) is the first identified endogenous selective estrogen receptor modulator. 27HC levels correlate well with that of cholesterol, and also rise progressively with age. 27HC affects estrogen receptor function by the antagonism of estrogen action and also by the direct modulation of the receptor function, and similar to estrogen/estrogen receptors, 27HC has many actions in various tissues...

Identification of the CETP, LIPG (encoding endothelial lipase) and APOC3 genes, and ana lysis of rare genetic variants in them, have allowed researchers to increase understanding of HDL metabolism significantly. However, development of cardiovascular risk-reducing therapeutics targeting the proteins encoded by these genes has been less straightforward. The failure of two CETP inhibitors is complex but illustrates a possible over-reliance on HDL cholesterol as a marker of therapeutic efficacy. The case of endothelial lipase exemplifies the importance of utilizing population-wide genetic studies of rare variants in potential therapeutic targets to gain information on cardiovascular disease end points...

The metabolic syndrome, a cluster of metabolic derangements that include obesity, glucose intolerance, dyslipidemia and hypertension, is a major risk factor for cardiovascular disease. Insulin resistance has been proposed to be the common feature that links obesity to the metabolic syndrome, but the mechanism remains obscure. Although the excess content of triacylglycerol in muscle and liver is highly associated with insulin resistance in these tissues, triacylglycerol itself is not causal but merely a marker...

ApoAII, the second most abundant protein of the human plasma HDLs, was discovered nearly 50 years ago. Over the subsequent years, nearly 2000 studies - epidemiological, cell-based, biochemical, mouse and human - have attempted to unravel its role in human lipid metabolism. On the basis of these studies, apoAII has been described as an activator and inhibitor of various plasma activities, and as both pro- and anti-atherogenic. Here, we summarize the studies of apoAII, use the preponderance of evidence to propose that the apoAII compass can be reset towards an antiatherogenic course, and suggest ways to stay the course...

The rising prevalence of obesity in the last few decades has been accompanied by an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD encompasses a spectrum of liver pathology from isolated hepatic steatosis to steatohepatitis and advanced fibrosis. Dietary habits characterized by consumption of high-caloric, lipid-rich diets play a major role in the development of NAFLD. Recent studies have uncovered the importance of certain components of the diet. In this review, we will focus on the growing evidence for a central role of n-6 polyunsaturated fatty acids...

Significant knowledge regarding different molecules involved in the transport of dietary fat into the circulation has been garnered. Studies point to the possibility that accumulation of intestine-derived lipoproteins in the plasma could contribute to atherosclerosis. This article provides a brief overview of dietary lipid metabolism and studies in mice supporting the hypothesis that intestinal lipoproteins contribute to atherosclerosis. Deficiencies in lipoprotein lipase and Gpihbp1, and overexpression of heparanse in mice, are associated with increases in atherosclerosis, suggesting that defects in catabolism of larger lipoproteins in the plasma contribute to atherosclerosis...

The cholesterol molecule is at the center of the pathophysiology of many vascular diseases. Whole-body cholesterol pools are maintained by a balance of endogenous synthesis, dietary absorption and elimination from our bodies. While the cellular aspects of cholesterol metabolism received significant impetus from the seminal work of Goldstein and Brown investigating LDL receptor trafficking, how dietary cholesterol was absorbed and eliminated was relatively neglected. The identification of the molecular defect a rare human disorder, Sitosterolemia, led to elucidation of a key mechanism of how we regulate the excretory pathway in the liver and in the intestine...

Diabetic retinopathy is the most disabling complication of diabetes, affecting 65% of patients after 10 years of the disease. Current treatment options for diabetic retinopathy are highly invasive and fall short of complete amelioration of the disease. Understanding the pathogenesis of diabetic retinopathy is critical to the development of more effective treatment options. Diabetic hyperglycemia and dyslipidemia are the main metabolic insults that affect retinal degeneration in diabetes. Although the role of hyperglycemia in inducing diabetic retinopathy has been studied in detail, much less attention has been paid to dyslipidemia...

Oxysterols are oxidized species of cholesterol that are derived from exogenous (e.g. dietary) and endogenous (in vivo) sources. Oxysterols play critical roles in normal physiologic functions as well as in pathophysiologic processes in a variety of organ systems. This review provides an overview of oxysterol biology from the vantage point of the biliary system. Several oxysterols have been identified in human bile in the context of biliary tract infection and inflammation. This finding has led to investigations regarding the potential pathophysiologic significance of biliary oxysterols in diseases affecting the biliary system, with an emphasis on cholangiocarcinoma...

Understanding the etiopathological processes of Alzheimer's disease (AD) in the preclinical and early clinical stages will be important in developing new therapeutic targets and biomarkers. There is growing consensus that nonamyloid targets will be necessary to reverse or slow AD progression. Lipidomic, metabolomic and targeted approaches have identified pathways and products of sphingolipid metabolism that are altered early in the course of AD and contribute to the neuropathological alterations associated with AD, including amyloid-β production, tau formation and neurodegeneration...