Abstract: Purpose of reviewThe present review summarizes the clinical development of adeno-associated viral vector (AAV)1-lipoprotein lipase (LPL)S447X gene therapy (alipogene tiparvovec) for lipoprotein lipase deficiency. Lipoprotein lipase deficiency is a rare inherited disease characterized by severe hyper

Abstract: Purpose of review Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease; we highlight the most recent research initiatives that have sought to define Lp(a)-dependent pathogenicity as well as pharmacologic approaches to lowering Lp(a). Recent findings Recent large-scale meta-analyses have confirmed elevated Lp(a) concentrations to be a moderate but consistent prospective coronary heart disease (CHD) risk factor. The Mendelian randomization approach has also associated LPA variants with Lp(a) concentration and CHD risk. Discoveries linking Lp(a) to oxidized phospholipid burden have implicated a proinflammatory role for Lp(a) hinting at a new mechanism underlying the association with CHD risk, which adds to previous atherogenic and thrombogenic mechanisms. Most existing Lp(a)-lowering drug treatments almost always show simultaneous effects on other lipoproteins, making it difficult to assign any clinical outcome specifically to the effects of Lp(a) lowering. Early experiments with antisense oligonucleotides targeting apolipoprotein(a) mRNA seem to indicate the pleiotropic effects of Lp(a) reduction on LDL and HDL in mice. The mechanism linking Lp(a) concentration with concentrations of other blood lipids remains unknown but may provide an insight into Lp(a) metabolism. Summary Despite the wealth of epidemiologic evidence supporting Lp(a) concentration as a CHD risk factor, the lack of a definitive functional mechanism involving an Lp(a)-dependent pathway in CHD pathogenesis has limited the potential clinical connotation of Lp(a). However, the application of novel technologies to the long-standing mysteries of Lp(a) biology seems to provide the opportunity for expanding our understanding of Lp(a) and its complex role in cardiovascular health.

Abstract: Purpose of review Plasma free fatty acids (FFA) are major substrates for hepatic VLDL-triglycerides (VLDL-TG) production. In addition, it is a common belief that VLDL-TG production is a substrate driven process primarily determined by systemic FFA delivery. This review summarizes recent research of our understanding of the regulation of VLDL-TG production. Recent findings Recent studies have shown that increasing FFA flux is not inevitably associated with increased VLDL-TG production. Exercise induced increase in FFA flux resulting in unchanged VLDL-TG production in lean patients as well as in obese patients with increased hepatic fat despite exercise reduced hepatic fat content. With respect to the other inseparable conditions of insulin resistance and hyperinsulinemia, recent studies demonstrate that increased hepatic VLDL-TG production precedes the insulin resistance-associated impairment of the regulation of hepatic glucose production, whereas isolated chronic hyperinsulinemia (insulinoma) was not associated with increased VLDL-TG production. Insulin has been shown to have acute potent temporary suppressing effect on VLDL-TG production and new data demonstrates that increased glucagon reduces VLDL-TG production. Finally, recent studies indicate that sex hormones, oestrogen and testosterone, have no or very modest impact on VLDL-TG production. Summary Regulation of hepatic VLDL-TG production involves interplay between systemic FFA delivery, hormonal, and nutritional factors that act in concert with hepatic fatty acid handling to regulate short-term and long-term VLDL-TG production. The results of recent studies underscore that our current understanding of these relationships is complex and needs further research.

Abstract: Purpose of review Bile acid sequestrants (BAS) have been used for more than 50 years in the treatment of hypercholesterolemia. The last decade, bile acids are emerging as integrated regulators of metabolism via induction of various signal transduction pathways. Consequently, BAS treatment may exert unexpected side-effects. We discuss a selection of recently published studies that evaluated BAS in several metabolic diseases. Recent findings Recently, an increasing body of evidence has shown that BAS in addition to ameliorating hypercholesterolemia are also effective in improving glycemic control in patients with type 2 diabetes, although the mechanism is not completely understood. Furthermore, some reports suggested using these compounds to modulate energy expenditure. Many of these effects have been related to the local effects of BAS in the intestine by directly binding bile acids in the intestine or indirectly by interfering with signaling processes. Summary A substantial effort is being made by researchers to fully define the mechanism by which BAS improve glycemic control in type 2 diabetic patients. A new challenge will be to confirm in clinical trials the recent discoveries coming from animal experiments suggesting a role for bile acids in energy metabolism.

Abstract: Purpose of review The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL and is an important therapeutic target for treating cardiovascular disease. Abundance of the LDLR is subject to both transcriptional and nontranscriptional control. Here, we highlight a new post-transcriptional mechanism for controlling LDLR function via ubiquitination of the receptor by the E3-ubiquitin ligase inducible degrader of the LDLR (IDOL). Recent findings IDOL is a recently identified transcriptional target of the liver X receptors. Acting as an E3-ubiquitin ligase IDOL promotes ubiquitination of the LDLR, thereby marking it for lysosomal degradation. The determinants required for degradation of the LDLR by IDOL have been largely identified. IDOL also targets two related lipoprotein receptors, the very low-density lipoprotein receptor and apolipoprotein E receptor 2. Despite several similarities, the IDOL, and PCSK9 pathways for controlling LDLR abundance seem independent of each other. Genome-wide association studies have recently identified IDOL as a locus influencing variability in circulating levels of LDL, thereby highlighting the possible role of IDOL in human lipoprotein metabolism. Summary Transcriptional induction of IDOL by liver X receptor defines a new post-transcriptional pathway for controlling LDLR abundance and LDL uptake independent of sterol regulatory element binding proteins. Targeting IDOL activity may offer a novel therapeutic approach complementary to statins for treating cardiovascular disease.

Abstract: Purpose of review The phospholipase A2 (PLA2) family of proteins includes lipolytic enzymes that liberate the sn-2 fatty acyl chains from phospholipids to yield nonesterified fatty acids and lysophospholipids. The purpose of this review is to discuss recent findings showing distinct roles of several of these PLA2 enzymes in inflammatory metabolic diseases such as diabetes and atherosclerosis. Recent findings The group 1B PLA2 digestion of phospholipids in the intestinal lumen facilitates postprandial lysophospholipid absorption, which suppresses hepatic fatty acid oxidation leading to increased VLDL synthesis, decreased glucose tolerance, and promotion of tissue lipid deposition to accentuate diet-induced hyperlipidemia, diabetes, and obesity. Other secretory PLA2s promote inflammatory metabolic diseases by generating bioactive lipid metabolites to induce inflammatory cytokine production, whereas the major intracellular PLA2s, cPLA2α, and iPLA2, generate arachidonic acid and lysophosphatic acid in response to extracellular stimuli to activate leukocyte chemotactic response. Summary Each member of the PLA2 family of enzymes serves a distinct role in generating active lipid metabolites that promote inflammatory metabolic diseases including atherosclerosis, hyperlipidemia, obesity, and diabetes. The development of specific drugs that target one or more of these PLA2 enzymes may be novel strategies for treatment of these chronic inflammatory metabolic disorders.

Abstract: Purpose of review This review highlights the diverse roles of the high-affinity HDL receptor scavenger receptor class B, type I (SR-BI) in the modulation of global cholesterol homeostasis and vascular cell function, and the potential implications of these processes in atherosclerosis. Recent findings SR-BI in the liver plays a critical role in reverse cholesterol transport and it dramatically impacts the characteristics of the HDL particle, and through reverse cholesterol transport it promotes an antiatherogenic lipid environment in the vascular wall. SR-BI in macrophages may influence their inflammatory phenotype. In endothelial cells, SR-BI mediates HDL-induced endothelial nitric oxide synthase activation and proliferation and migration, and in platelets SR-BI may be prothrombotic in the setting of dyslipidemia. Several polymorphisms of SR-BI have been reported in humans that influence receptor expression or function. Summary In addition to regulating global lipid metabolism, SR-BI influences the functions of a variety of vascular cells relevant to atherosclerosis. Studies of SR-BI genetics in humans partially support the conclusions drawn from experimental models. However, because of the multiple functions of SR-BI, the diversity of cell types in which it is expressed, and the influence of the receptor on the characteristics of its own ligand, our understanding of the biology of the receptor is just emerging.

Abstract: Purpose of review The finding that brown adipose tissue (BAT) is present in adults brought BAT physiology into the focus of many researchers interested in energy metabolism. Here, we review recent insight into how BAT develops, functions and might help to treat metabolic disorders in humans. Recent findings BAT is under control of the nervous system, and several pathways have been identified that allow direct manipulation of BAT biology. In addition, some brown adipocytes arise from a distinct subset of white adipocyte precursors and studies were performed that characterize the development of these 'brite' adipocytes. Importantly, progress has been made in understanding how BAT takes up and dissipates nutrients that in metabolic disorders are present in excess. Finally, as it seems that BAT activity declines with age and obesity, we review findings that might shed light on how humans could sustain or increase BAT activity, thus preventing or treating obesity, hyperlipidemia and type 2 diabetes. Summary BAT is a powerful organ that controls the development of metabolic disease. These powers are boosted by mechanisms that turn white into brown fat and enhance lipid flux into BAT. However, in humans, it remains unclear what was the first: metabolic disease or decreased BAT activity.

Abstract: Purpose of reviewThe process of reverse cholesterol transport (RCT) is critical for disposal of excess cholesterol from the body. Although it is generally accepted that RCT requires biliary secretion, recent studies show that RCT persists in genetic or surgical models of biliary insufficiency. Disco

Abstract: Purpose of review Atherosclerosis is driven by cardiovascular risk factors that cause the recruitment of circulating immune cells beneath the vascular endothelium. Infiltrated monocytes differentiate into different macrophage subtypes with protective or pathogenic activities in vascular lesions. We discuss current knowledge about the molecular mechanisms that regulate lesional macrophage proliferation and apoptosis, two processes that occur during atherosclerosis development and regulate the number and function of macrophages within the atherosclerotic plaque. Recent findings Lesional macrophages in early phases of atherosclerosis limit disease progression by phagocytizing modified lipoproteins, cellular debris and dead cells that accumulate in the plaque. However, macrophages in advanced lesions contribute to a maladaptive, nonresolving inflammatory response that can lead to life-threatening acute thrombotic diseases (myocardial infarction or stroke). Macrophage-specific manipulation of genes involved in cell proliferation and apoptosis modulates lesional macrophage accumulation and atherosclerosis burden in mouse models, and studies are beginning to elucidate the underlying mechanisms. Summary Despite recent advances in our understanding of macrophage proliferation and apoptosis in atherosclerotic plaques, it remains unclear whether manipulating these processes will be beneficial or harmful. Advances in these areas may translate into more efficient therapies for the prevention and treatment of atherothrombosis.

Abstract: PURPOSE OF REVIEW In recent years, many of the concerns surrounding the glycemic index have been addressed by methodological studies and clinical trials comparing diets carefully matched for other nutrients. These findings are reviewed together with new observational evidence for the role of the dietary glycemic index in the etiology of cardiovascular disease. RECENT FINDINGS The determination and classification of the glycemic index of a food product is now standardized by the International Standards Organization. Systematic studies using isoenergetic single and mixed meals have shown that glycemic index and/or glycemic load are stronger predictors of postprandial glycemia and insulinemia than carbohydrate content alone. In overweight individuals, a diet that combined modestly higher protein and lower glycemic index carbohydrates was the most effective diet for prevention of weight regain. New observational studies have reported increased risks of coronary heart disease associated with higher intakes of carbohydrates from high glycemic index foods. Epidemiological evidence has emerged linking dietary glycemic index to visceral fat and inflammatory disease mortality. SUMMARY There is growing recognition that replacing saturated fat with refined, high glycemic index carbohydrates increases postprandial glycemia and may be detrimental for weight control and predisposition to cardiovascular and inflammatory disease. In contrast, low glycemic index carbohydrates reduce risk.

Abstract: Purpose of review Recent epidemiological and genetic studies have suggested that lipoprotein (a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD). There is now interest in evaluating Lp(a) as a therapeutic target. This review will summarize emerging therapeutic agents to lower Lp(a). Recent findings Apheresis is the most efficacious method to lower Lp(a). Currently, there are no approved drugs to specifically lower Lp(a). However, recent data has demonstrated that Lp(a) can be significantly lowered, along with reductions in other apolipoprotein B-100 (apoB) containing lipoproteins, with antisense oligonucleotides to apoB, monoclonal antibodies to proprotein convertase subtilisin/kexin type 9, cholesterol ester transfer protein inhibitors, and thyromimetics. The farnesoid X receptor/fibroblast growth factor axis and interleukin-6 also influence Lp(a) levels and may be targets of therapy. Finally, specific apolipoprotein (a) [apo(a)] inhibitors apo(a) have been developed and reduce apo(a) mRNA and protein levels up to 86% without significantly affecting other lipoproteins. Summary Lp(a) remains the last major lipoprotein disorder without any specific therapy. With the strong and accumulating data on its role as a causal risk factor for CVD, a rationale exists to develop novel agents to reduce Lp(a) and test the hypothesis that this will lead to reduced CVD events.

Abstract: Purpose of review We summarize recent progress on GPIHBP1, a molecule that transports lipoprotein lipase (LPL) to the capillary lumen, and discuss several newly studied molecules that appear important for the regulation of LPL activity.

Abstract: Purpose of reviewDifferences in local blood flow patterns along the endothelium may trigger abnormal vascular responses which can have profound pathophysiological consequences. While endothelial cells exposed to laminar blood flow (high shear stress) are protected from atherosclerosis formation, tur

Abstract: Purpose of review A negative correlation between HDL cholesterol levels and risk of coronary artery disease has long been recognized. Emerging knowledge of the molecular speciation and functional properties of HDL provides an opportunity to study the atheroprotective effects of specific metabolic processes. The discovery of the quantum particle among the molecular species of HDL (prebeta-1 HDL) and its role in cholesterol efflux from the artery wall, offer a means of assessing the efficiency of efflux. This review presents observations on the structure and metabolism of this particle and its emerging role as a predictor of risk for atherosclerotic vascular disease. Recent findings Prebeta-1 HDL is now recognized as the primary acceptor of cholesterol effluxed by the dominant ATP-binding cassette A1 (ABCA1) transporter in arterial macrophages, a critical step in reverse cholesterol transport. Several studies have revealed an association between high levels of this particle and risk of globally defined coronary artery disease and carotid intima-media thickness. Recently, these findings have been confirmed and extended to include myocardial infarction. High levels of prebeta-1 HDL may serve as an index of functional impairment of cholesterol efflux or esterification, either of which would be expected to impede reverse cholesterol transport. Summary Recent studies underscore the critical role of prebeta-1 HDL in reverse cholesterol transport and its use as a marker of risk for structural coronary disease, myocardial infarction, and cerebral vascular disease.

Abstract: Purpose of reviewEndothelial dysfunction plays an important role in development and progression of atherosclerosis and may also contribute to the pathogenesis of type 2 diabetes. This review summarizes recent findings on the effects of vitamin D, antioxidant vitamins, polyphenols, polyphenol-rich fo

Abstract: Purpose of review The varied effects of colony-stimulating factors (CSFs) on monocytes and macrophages during inflammation and atherosclerosis and its clinical presentation prompt the question whether the differing effects of CSFs dictate macrophage function and disease progression. Recent findings CSFs can give rise to heterogeneous populations of monocyte-derived macrophages that are characterized by disparate expression of distinct molecules which dictate their ability to process lipid and regulate inflammatory and immune responses. The CSFs have been found within atherosclerotic plaques and in the circulation where their levels may act as predictive biomarkers of disease progression. Accordingly, differing exposure to these factors imparts divergent genomic signatures and functional properties on macrophages and may impact the multifactorial steps involved in atherogenesis, plaque progression and instability. Summary Great interest in macrophage heterogeneity in the genesis and progression of atherosclerosis has led to the search for consistent markers of specific subsets in both animal models and humans. A better understanding of the overlap and competition between CSF regulation of macrophage phenotypes is therefore warranted, to allow their characterization in plaques. Subsequent targeted genetic and pharmacological intervention will facilitate the generation of therapeutic approaches to halt the progression and rupture of advanced atherosclerotic plaques.

Abstract: PURPOSE OF REVIEW This article reviews the mechanisms leading to the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) and the effects of hypoglycaemic and lipid-lowering therapies on NAFLD/NASH. RECENT FINDINGS The interaction of lipogenesis, fatty acid oxidation, inflammation, endoplasmic reticulum stress and hepatic insulin resistance contribute to the pathogenesis of NAFLD/NASH. Few large scale clinical trials exist with biopsy or magnetic resonance endpoints as opposed to ultrasonographic and transaminase endpoints. Trial evidence that exists supports the utility of weight loss, metformin, thiazolidinediones, fibrates, niacin, ezetimibe and statins in improving the steatosis component of NAFLD/NASH though with less or minimal effects on the fibrotic component of NASH. SUMMARY Hypoglycaemic and lipid-lowering therapies may have a role in the treatment of NAFLD/NASH but large scale endpoint trials remain to be performed.

Abstract: Purpose of reviewOver the past several years, many more isoforms for the same enzymes, specifically for 1-acylglycerol-3-phosphate O-acyltransferases (AGPATs), have been cloned and studied In this review, we summarize their biochemical features and discuss their functional roleRecent findingsThe m

Abstract: PURPOSE OF REVIEW Type 2 diabetes mellitus (T2DM) and related syndromes exhibit a deadly triad of dyslipoproteinemia, which leads to atherosclerosis, hyperglycemia, which causes microvascular disease, and hypertension. These features share a common, but unexplained, origin--namely, pathway-selective insulin resistance and responsiveness (SEIRR). Here, we review recent work on hepatic SEIRR indicating that deranged insulin signaling may have a remarkably simple molecular basis. RECENT FINDINGS Comprehensive examination of a set of 18 insulin targets revealed that T2DM liver in vivo exhibits a specific defect in the ability of the NAD(P)H oxidase 4 (NOX4) to inactivate protein tyrosine phosphatase gene family members after stimulation with insulin, and that impairment of this single molecule, NOX4, in cultured hepatocytes recapitulates all features of hepatic SEIRR in vivo. These features include insulin-stimulated generation of an unusual monophosphorylated form of AKT at Thr308 (pT308-AKT) with only weak phosphorylation at Ser473, impaired insulin-stimulated pathways for lowering plasma levels of lipids and glucose, but continued lipogenic pathways and robust extracellular signal-regulated kinase activation. This new study, in combination with important prior work, provides clues to several long-standing mysteries, such as how AKT might regulate lipid-lowering and glucose-lowering pathways that become insulin-resistant but also lipogenic pathways that remain insulin-responsive, as well as a potential role for NOX4 in insulin-stimulated generation of oxysterol ligands for LXR, a key lipogenic factor. SUMMARY These findings suggest a unified molecular explanation for fatty liver, atherogenic dyslipoproteinemia, hyperglycemia, and hence accelerated atherosclerosis and microvascular disease in T2DM, obesity, and related syndromes of positive caloric imbalance.

Abstract: Purpose of review In prediabetes and diabetes, hyperglycemia is often accompanied by fasting and postprandial hyperlipidemia. Incretin-based therapies are in increasing clinical use for treating hyperglycemia, but recent evidence emphasizes their ability to improve lipoprotein abnormalities. This is significant as heightened postprandial chylomicron levels during insulin resistance contribute to atherogenic diabetic dyslipidemia. This review summarises the evidence supporting a beneficial effect of incretin-based therapies on diabetic dyslipidemia through modulation of intestinal lipoprotein metabolism. Recent findings Preclinical and clinical trials have involved administering dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists to healthy and insulin-resistant individuals. Results indicate that enhancing GLP-1R signalling decreases postprandial apoB48-containing triglyceride-rich lipoproteins. These effects may be direct or may be secondary to reduced gastric emptying, increased insulin secretion, or enhanced chylomicron clearance. Summary Enhancing GLP-1R activity improves intestinal lipoprotein metabolism. GLP-1-mediated control of postprandial chylomicron production may be lost in type 2 diabetes in which the incretin response is impaired and in which associated dyslipidemia involves an excess of atherogenic chylomicron remnants. Further human studies are needed to better establish the impact of incretin-based therapies on dyslipidemia, as this offers a major new therapeutic approach to reduce cardiovascular risk in type 2 diabetic patients.

Abstract: PURPOSE OF REVIEW Noncholesterol sterols (NCSs) in plasma encompass endogenous cholesterol precursors and exogenous phytosterols and cholesterol metabolites, which are used as surrogate measures of cholesterol synthesis and cholesterol absorption, respectively. The ratios of cholesterol synthesis to cholesterol absorption surrogates are also utilized to assess the overall balance of cholesterol metabolism, with higher values representing more synthesis and lower values more absorption. The objective of this review is to focus on recent findings using plasma NCSs and their potential in customizing dietary and pharmacological hypolipidemic therapies. RECENT FINDINGS NCSs are often used to assess the impact of pharmacological and dietary interventions on cholesterol metabolism. Various forms of dyslipidemia have been characterized using NCSs, and NCSs may be a valuable tool in selecting appropriate treatment therapies. NCSs levels are affected by genetic, dietary and physiological factors and have been related to cardiovascular disease risk. SUMMARY The expanded use of plasma NCSs is currently limited by the lack of standardized methodology. However, noncholesterol sterols are still a valuable research tool for the overall assessment of cholesterol metabolism and may have clinical potential in the personalization of diet and medicine.

Abstract: Purpose of review: The fish fatty acids eicosapentenoic acid (EPA) and docosahexenoic acid (DHA) may be protective against fatal coronary heart disease (CHD) and sudden cardiac death. This review summarizes the recent findings of prospective cohort studies and randomized controlled trials. Recent findings: A recently published meta-analysis of 17 prospective cohort studies showed that eating fish once a week compared to eating less fish was associated with a 16% lower risk of fatal CHD. Epidemiologic studies with cardiac arrest or sudden cardiac death as endpoint observed also an inverse relation with fish consumption. In contrast, a recently published meta-analysis of 14 randomized, double-blind, placebo-controlled trials in cardiovascular patients did not show a protective effect of an additional amount of EPA-DHA on fatal CHD and sudden cardiac death. Subgroup analyses suggested that this could be because of a low absolute risk as a consequence of the state-of-the-art drug treatment. Summary: Eating fatty fish once or lean fish twice a week is recommended for both primary and secondary prevention of CHD. A definite statement cannot be made about the dosage of EPA-DHA required for secondary prevention of CHD

Abstract: A number of animal studies have yielded data suggesting that postprandial hyperlipidemia can be atherogenic. Also, chylomicrons, like VLDL, have been demonstrated in human arterial lesions. Many animals secrete apoB-48, the principal protein of chylomicrons, from the liver as well as from the intestine. Determining the contribution of particles of intestinal origin is difficult in these models, as opposed to humans in whom the apoB-48 protein is secreted only from the intestine. The extent to which chylomicrons contribute to atherogenesis in humans is beginning to emerge. Relatively few studies have used the categorical marker, apoB-48, to identify the singular contribution of chylomicrons in patients with postprandial hyperlipidemia. Also, there can be a significant increase of secretion of triglyceride-rich VLDL from liver during the postprandial period [1 & ]. Masuda et al. [2 && ] have demonstrated a significant correlation between plasma apoB-48 levels and severity of coronary atherosclerosis determined by cardiac catheterization. Observations that extend this relationship to the cerebral vasculature include a study demonstrating elevated plasma levels of apoB-48 associated with atherothrombotic stroke [3 && ], and one relating apoB-48 levels to intima media thickness in major cerebral vessels [4]. Awareness of the involvement in atherogenesis of chylomicrons, and probably to a greater extent their remnants, lends importance to the role that the liver sinusoidal cells play in regulating the rate of hepatic uptake of chylomicron remnants [5 && ]. Biochemistry and Biophysics, Cardiovascular Research Institute, University of California Medical Center, San Francisco, California, USA

Abstract: Purpose of reviewThe success of high throughput sequencing programmes, including the Human Genome Project led to the ‘identification’ of a large number of novel genes of completely unknown function. Since then, many of these genes have been subject to functional studies focussed on uncovering their

Abstract: Purpose of reviewFamilial hypercholesterolemia is characterized by a major elevation in circulating LDL-cholesterol levels, cholesterol deposition within the arterial wall and an increased risk of premature coronary artery disease. The reverse cholesterol transport (RCT) is now considered as a key p

Abstract: Purpose of reviewTo offer a comprehensive overview of the best available evidence linking vitamin D status, including the effect of vitamin D supplementation, to the risk of cardiovascular events.Recent findingsThere is an abundance of plausible mechanisms by which vitamin D might have a favorable e

Abstract: Purpose of reviewPerturbations in fatty acid levels and in regulatory proteins linked to fat and mitochondrial homeostasis are associated with modifying the risk of Parkinson's disease . Findings, that are not surprising, based on the high fat content of the brain, the myriad of neurological functio