Abstract：
PURPOSE OF REVIEW:Several members of the fibroblast growth factor (FGF) family have been identified as key regulators of energy metabolism in rodents and nonhuman primates. Translational studies show that their metabolic actions are largely conserved in humans, which led to the development of various FGF-based drugs, including FGF21-mimetics LY2405319, PF-05231023, and pegbelfermin, and the FGF19-mimetic NGM282. Recently, a number of clinical trials have been published that examined the safety and efficacy of these novel therapeutic proteins in the treatment of obesity, type 2 diabetes (T2D), nonalcoholic steatohepatitis (NASH), and cholestatic liver disease. In this review, we discuss the current understanding of FGFs in metabolic regulation and their clinical potential. RECENT FINDINGS:FGF21-based drugs induce weight loss and improve dyslipidemia in patients with obesity and T2D, and reduce steatosis in patients with NASH. FGF19-based drugs reduce steatosis in patients with NASH, and ameliorate bile acid-induced liver damage in patients with cholestasis. In contrast to their potent antidiabetic effects in rodents and nonhuman primates, FGF-based drugs do not appear to improve glycemia in humans. In addition, various safety concerns, including elevation of low-density lipoprotein cholesterol, modulation of bone homeostasis, and increased blood pressure, have been reported as well. SUMMARY:Clinical trials with FGF-based drugs report beneficial effects in lipid and bile acid metabolism, with clinical improvements in dyslipidemia, steatosis, weight loss, and liver damage. In contrast, glucose-lowering effects, as observed in preclinical models, are currently lacking.
journal_name
Curr Opin Lipidoljournal_title
Current opinion in lipidologyauthors
Struik D,Dommerholt MB,Jonker JWdoi
10.1097/MOL.0000000000000599subject
Has Abstractpub_date
2019-06-01 00:00:00pages
235-243issue
3eissn
0957-9672issn
1473-6535journal_volume
30pub_type
杂志文章,评审abstract：PURPOSE OF REVIEW:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and it has overlapping pathogenesis with diabetes and cardiovascular disease. Reviewed here are recent advances in understanding the contribution of diet and selected nutrients to NAFLD. RECENT FINDINGS:To und...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000043
更新日期：2014-02-01 00:00:00
abstract：PURPOSE OF REVIEW:The science and policy of functional foods are a matter of global concern and this review provides up-to-date information about the Japanese 'food for specified health use' policy based on functional food science. RECENT FINDINGS:A great many studies on nonnutritive but physiologically functional foo...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e3282f3f505
更新日期：2008-02-01 00:00:00
abstract：PURPOSE OF REVIEW:It is well accepted that LDLs and its modified form oxidized-LDL (ox-LDL) play a major role in the development of atherosclerosis and foam cell formation. Whereas the majority of these cells have been demonstrated to be derived from macrophages, smooth muscle cells (SMCs) give rise to a significant nu...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000113
更新日期：2014-10-01 00:00:00
abstract：:Oxidatively damaged LDL may play a critical role in the pathogenesis of atherosclerotic vascular disease. Several pathways promote LDL oxidation in vitro but the physiologically relevant mechanisms have proven difficult to identify. Detection of stable compounds that result from specific reaction pathways has provided...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199710000-00005
更新日期：1997-10-01 00:00:00
abstract：PURPOSE OF REVIEW:Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly identified in most severe cases. Triglycerides are generally considered as 'bystanders' for cardiovascular diseases. However, biological an...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000622
更新日期：2019-08-01 00:00:00
abstract：PURPOSE OF REVIEW:Hypoxia triggers various cellular processes, both in physiological and pathological conditions, and has recently also been implicated in atherosclerosis. This review summarizes the recent evidence for the presence and the role of hypoxia in atherosclerosis. Additionally, it will elucidate on hypoxic s...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e32836484a4
更新日期：2013-10-01 00:00:00
abstract：PURPOSE OF REVIEW:This review examines recent evidence proposing that lipids and lipoproteins can act as nuclear factors regulating chromatin structure. These novel data broaden our understanding of the mechanisms by which lipoproteins can affect basic biological phenomena such as transcription, genome stability, and c...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/01.mol.0000180165.70077.ee
更新日期：2005-10-01 00:00:00
abstract：PURPOSE OF REVIEW:Capsaicin and its nonpungent analog (capsinoids) are known to be food ingredients that increase energy expenditure and decrease body fat. This article reviews the role of brown adipose tissue (BAT) for the thermogenic effect of these compounds in humans and proposes the possibility of some other antio...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e32835a4f40
更新日期：2013-02-01 00:00:00
abstract：:The Smith-Lemli-Opitz syndrome is a disorder of morphogenesis resulting from an enzymatic defect in the last step of cholesterol metabolism (reduction of 7-dehydrocholesterol). Analysis of the defective gene and identification of mutations therein have paved the way for the study of the molecular genetics of the disor...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199904000-00006
更新日期：1999-04-01 00:00:00
abstract：PURPOSE OF REVIEW:Mesenchymal stem cells (or multipotent stromal cells) are emerging as a potent cell type for cardiac cell therapy. This review describes the potential of cardiac mesenchymal stem cell therapy, but also highlights some recently discovered less favorable mesenchymal stem cell characteristics. RECENT FI...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e3282f0dd1f
更新日期：2007-12-01 00:00:00
abstract：PURPOSE OF REVIEW:Fatty acid transport proteins are a family of proteins involved in fatty acid uptake and activation. This review summarizes recent progress in elucidating the function of fatty acid transport proteins. RECENT FINDINGS:Recent experiments clearly establish FATP1 as a regulated fatty acid transporter in...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e3281338558
更新日期：2007-06-01 00:00:00
abstract：:A site-specific cytidine deamination (cytidine to uridine) in nuclear apolipoprotein B messenger RNA creates a translational stop codon that produces apolipoprotein B48. This process is mediated by an enzyme composed of distinct subunits, including apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-1 ...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199504000-00002
更新日期：1995-04-01 00:00:00
abstract：:Lipid-poor apolipoproteins remove cellular cholesterol and phospholipids by an active transport pathway controlled by an ATP binding cassette transporter called ABCA1 (formerly ABC1). Mutations in ABCA1 cause Tangier disease, a severe HDL deficiency syndrome characterized by a rapid turnover of plasma apolipoprotein A...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-200006000-00005
更新日期：2000-06-01 00:00:00
abstract：PURPOSE OF REVIEW:Phospholipids are major constituents in the intestinal lumen after meal consumption. This article highlights current literature suggesting the contributory role of intestinal phospholipid metabolism toward cardiometabolic disease manifestation. RECENT FINDINGS:Group 1b phospholipase A2 (PLA2g1b) cata...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000334
更新日期：2016-10-01 00:00:00
abstract：:The cytokines interleukin-1 and tumor necrosis factor contribute to the pathogenesis of inflammatory diseases and, potentially, to atherogenesis. The synthesis of these cytokines in humans can be suppressed by oral intake of n-3 polyunsaturated fatty acids. This mechanism may contribute to the beneficial effect of lon...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199602000-00011
更新日期：1996-02-01 00:00:00
abstract：:The present review summarizes recent advances in the transcriptional regulation of the human apolipoprotein genes, focusing mostly, but not exclusively, on in-vivo studies and signaling mechanisms that affect apolipoprotein gene transcription. An attempt is made to explain how interactions of transcription factors tha...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-200104000-00012
更新日期：2001-04-01 00:00:00
abstract：PURPOSE OF REVIEW:We review stable isotope tracer studies of apolipoprotein B-100 (apoB) kinetics concerning genetic polymorphisms and mutations that affect human lipoprotein metabolism. RECENT FINDINGS:In obese men, the allelic combination of the apoB signal peptide, SP24, and cholesteryl ester transfer protein, CETP...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e3283378e5a
更新日期：2010-04-01 00:00:00
abstract：PURPOSE OF REVIEW:Although the role for microRNAs (miRNAs) in regulating multiple physiological processes including apoptosis, cell differentiation, and cancer is well established, the importance of these tiny RNAs in regulating lipid metabolism has only recently been uncovered. This review summarizes the evidence for ...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e3283428d9d
更新日期：2011-04-01 00:00:00
abstract：:Familial combined hyperlipidaemia is the most common inherited hyperlipidaemia and is found in up to 10% of patients with premature myocardial infarction. The genetic and metabolic bases of the disorder have not yet been defined. This review discusses the important advances in the past year in our understanding of the...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199806000-00002
更新日期：1998-06-01 00:00:00
abstract：PURPOSE OF REVIEW:Proprotein convertase subtilisin kexin type 9 (PCSK9) acts as an endogenous natural inhibitor of the LDL receptor pathway, by targeting the receptor to lysosomes for degradation. Beside the liver, PCSK9 is also expressed at significant levels in other tissues, where its function remains unclear. The c...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000180
更新日期：2015-06-01 00:00:00
abstract：PURPOSE OF REVIEW:The current review considers what we have learnt from the clinical outcome trials with the cetrapibs; the inhibitors of cholesteryl ester transfer protein that increase HDL cholesterol levels; torcetrapib, dalcetrapib, evacetrapib and anacetrapib. RECENT FINDINGS:Although an off-target increase in bl...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000518
更新日期：2018-08-01 00:00:00
abstract：PURPOSE OF REVIEW:The endoplasmic reticulum (ER) maintains cellular metabolic homeostasis by coordinating protein synthesis, secretion activities, lipid biosynthesis and calcium (Ca²⁺) storage. In this review, we will discuss how altered ER homeostasis contributes to dysregulation of hepatic lipid metabolism and contri...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000056
更新日期：2014-04-01 00:00:00
abstract：PURPOSE OF REVIEW:To summarize the recent studies directly comparing LDL and lipoprotein(a) as causal factors for cardiovascular disease and mortality. RECENT FINDINGS:In approximately 100,000 individuals from the Copenhagen General Population Study for risk of myocardial infarction, in observational analyses per 39 m...
journal_title：Current opinion in lipidology
pub_type： 杂志文章
doi：10.1097/MOL.0000000000000681
更新日期：2020-06-01 00:00:00
abstract：PURPOSE OF REVIEW:Brown adipose tissue (BAT) is an emerging target to combat cardiometabolic disorders as it can take up substantial amounts of glucose and lipids from the circulation for heat production. This review focuses on new concepts in BAT physiology and discusses the need for new techniques to determine BAT ac...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000296
更新日期：2016-06-01 00:00:00
abstract：PURPOSE OF REVIEW:Familial hypercholesterolaemia is a hereditary disorder of lipoprotein metabolism which causes a lifelong increase in LDL-C levels resulting in premature coronary heart disease. The present review looks at some of the recent literature on how molecular methods can be used to assist in the definitive d...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0000000000000430
更新日期：2017-08-01 00:00:00
abstract：PURPOSE OF REVIEW:The purpose of this review is to present recent information on lipid lowering in diabetes mellitus. New information from randomized clinical trials will be discussed together with implications for clinical practice. Residual risk persists despite statin therapy and additional approaches, particularly ...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/MOL.0b013e328314b6b4
更新日期：2008-12-01 00:00:00
abstract：PURPOSE OF REVIEW:To provide an update on clinical trials of gene therapy for atherosclerotic cardiovascular disease published since 1 August 2001 and summarize the general advantages and potential problems of gene transfer in these disorders. RECENT FINDINGS:There are two major areas in which gene therapy has entered...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-200212000-00009
更新日期：2002-12-01 00:00:00
abstract：:The microsomal triglyceride transfer protein is necessary for the assembly and secretion of lipoproteins containing apolipoprotein B. During the past year, significant progress has been made towards understanding the role of microsomal triglyceride transfer protein in lipoprotein assembly at both a cellular and molecu...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199706000-00002
更新日期：1997-06-01 00:00:00
abstract：:The plasminogen and coagulation systems have been extensively characterized at the biochemical level. Recent gene targeting and gene transfer studies have provided novel insights into their role in the formation of blood vessels and in the pathogenesis of blood vessel disorders including thrombosis, restenosis and ath...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199704000-00010
更新日期：1997-04-01 00:00:00
abstract：:Further understanding of the causative link between plasma lipids and coronary heart disease will come from a deeper appreciation of the impact of lipoprotein heterogeneity on the processes of atherosclerosis and thrombosis. It is now widely appreciated that remnants of triglyceride-rich lipoproteins, IDL and specific...
journal_title：Current opinion in lipidology
pub_type： 杂志文章,评审
doi：10.1097/00041433-199906000-00006
更新日期：1999-06-01 00:00:00
