Yanan Wang

Yanan Wang
Leiden University Medical Centre | LUMC · Department of Endocrinology

PhD

About

117
Publications
8,064
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1,720
Citations
Citations since 2017
70 Research Items
1371 Citations
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2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
Introduction

Publications

Publications (117)
Article
Full-text available
Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced m...
Article
Full-text available
Objectives Studies in mice have recently linked increased dietary choline consumption to increased incidence of obesity-related metabolic diseases, while several clinical trials have reported an anti-obesity effect of high dietary choline intake. Since the underlying mechanisms by which choline affects obesity are incompletely understood, the aim o...
Article
Full-text available
Analogues of the hepatokine FGF21 are in clinical development for type 2 diabetes and nonalcoholic steatohepatitis (NASH) treatment. Although their glucose-lowering and insulin-sensitizing effects have been largely unraveled, the mechanisms by which they alleviate liver injury have only been scarcely addressed. Here, we aimed to unveil the mechanis...
Article
Full-text available
Within the human population, considerable variability exists between individuals in their susceptibility to develop obesity and dyslipidemia. In humans, this is thought to be caused by both genetic and environmental variation. APOE*3-Leiden.CETP mice, as part of an inbred mouse model in which mice develop the metabolic syndrome upon being fed a hig...
Article
Full-text available
Overconsumption of carbohydrate-rich food combined with adverse eating patterns contributes to the increasing incidence of metabolic syndrome (MetS) in China. Therefore, we conducted a randomized trial to determine the effects of a low-carbohydrate diet (LCD), an 8-h time-restricted eating (TRE) schedule, and their combination on body weight and ab...
Article
Full-text available
Background and aims Choline has been shown to exert atherogenic effects in Apoe−/− and Ldlr−/− mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the liver into the proinflammatory metabolite trimethylamine-N-oxide (TMAO). Since butyrate beneficially modulates the gut microbiota and has anti-inflammatory...
Preprint
Full-text available
Analogues of the hepatokine FGF21 are in clinical development for type 2 diabetes and nonalcoholic steatohepatitis (NASH) treatment. Although their glucose-lowering and insulin-sensitizing effects have been largely unraveled, the mechanisms by which they alleviate liver injury have only been scarcely addressed. Here, we aimed to unveil the mechanis...
Preprint
Full-text available
Objectives Studies in mice have recently linked increased dietary choline consumption to increased incidence of obesity-related metabolic diseases, while several clinical trials have reported an anti-obesity effect of high dietary choline intake. Since the underlying mechanisms by which choline affects obesity are incompletely understood, the aim o...
Article
Full-text available
Background: Feed efficiency (FE) is an important trait for livestock and humans. While the livestock industry focuses on increasing FE, in the current obesogenic society it is more of interest to decrease FE. Hence, understanding mechanisms involved in the regulation of FE and particularly how it can be decreased would help tremendously in counter...
Article
Full-text available
Aims Fibroblast growth factor (FGF) 21, a key regulator of energy metabolism, is currently evaluated in humans for treatment of type 2 diabetes and non-alcoholic steatohepatitis. However, the effects of FGF21 on cardiovascular benefit, particularly on lipoprotein metabolism in relation to atherogenesis, remain elusive. Methods and results Here,...
Article
Full-text available
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, by increasing hepatic low density lipoprotein (LDL) receptor (LDLR) levels, has emerged as a strategy to reduce atherosclerosis by lowering circulating very low density lipoprotein (VLDL)-cholesterol. We hypothesized that the therapeutic effectiveness of PCSK9 inhibition can be incre...
Article
Full-text available
Pharmacological blockade of the cannabinoid type 1 receptor (CB1R), a G-protein coupled receptor expressed in the central nervous system and in various peripheral tissues, reverses diet-induced obesity and dyslipidemia through the reduction of food intake and altered nutrient partitioning. This strategy is being explored for a number of therapeutic...
Article
Objective Brown fat activation attenuates atherosclerosis development by accelerating triglyceride-rich lipoprotein turnover and/or stimulation of reverse cholesterol transport via the SRB1 (scavenger receptor class B type 1). The aim of this study was to investigate the specific role of hepatic SRB1 in the atheroprotective properties of brown fat...
Article
Background: The high-density lipoprotein (HDL) hypothesis of atherosclerosis has been challenged by clinical trials of cholesteryl ester transfer protein (CETP) inhibitors which failed to show significant reductions in cardiovascular events. Plasma levels of HDL-cholesterol (HDL-C) decline drastically during sepsis and this phenomenon is explained,...
Article
Full-text available
Artificial light exposure is associated with dyslipidemia in humans, which is a major risk factor for the development of atherosclerotic cardiovascular disease. However, it remains unclear whether artificial light at night can exacerbate atherosclerosis. In this study, we exposed female APOE*3-Leiden.CETP mice, a well-established model for human-li...
Article
Full-text available
Background: Brown adipose tissue (BAT) is present in humans and rodents, and contributes to energy expenditure by converting energy stored in lipids and glucose into heat. Beta adrenergic receptor (β-AR) agonists have been proposed as pharmacological tools to activate BAT, but they lack selectivity for this tissue. This study aimed to investigate...
Article
Raising HDL using cholesteryl ester transfer protein (CETP) inhibitors failed to show a clinically relevant risk reduction of cardiovascular disease in clinical trials, inviting reconsideration of the role of CETP and HDL in human physiology. Based on solid evidence from studies with isolated macrophages, rodents, and humans, we propose that a majo...
Article
Full-text available
Aims: Brown fat activation accelerates the uptake of cholesterol-enriched remnants by the liver and thereby lowers plasma cholesterol, consequently protecting against atherosclerosis development. Hepatic cholesterol is then converted into bile acids (BAs) that are secreted into the intestine and largely maintained within the enterohepatic circulat...
Article
Obesity is taking worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar AMP-DNM which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here we show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in...
Article
Significance Lipid metabolism is crucial to many (patho-)physiological processes, including inflammation. In particular, cholesterol biosynthesis has emerged as an exciting novel therapeutic target in numerous recent studies. Much is known about the early steps in cholesterol biosynthesis; however, the later steps have hitherto largely been neglect...
Article
Full-text available
Cholesteryl ester transfer protein (CETP) is mainly expressed by Kupffer cells in the liver. A reduction of hepatic triglyceride content (HTGC) by pioglitazone or caloric restriction is accompanied by a decrease in circulating CETP. Since GLP-1 analogues also reduce HTGC, we assessed whether liraglutide decreases CETP. Furthermore, we investigated...
Article
Full-text available
Background: A positive energy balance is considered to be the primary cause of the development of obesity-related diseases. Treatment often consists of a combination of reducing energy intake and increasing energy expenditure. Here we use an existing computational modelling framework describing the long-term development of Metabolic Syndrome (MetS...
Article
According to the current dogma, cholesteryl ester transfer protein (CETP) decreases high-density lipoprotein (HDL)-cholesterol (C) and increases low-density lipoprotein (LDL)-C. However, detailed insight into the effects of CETP on lipoprotein subclasses is lacking. Therefore, we used a Mendelian randomization approach based on a genetic score for...
Article
Rationale: High-density lipoprotein cholesterol (HDL-C) levels decline during sepsis, and lower levels are associated with worse survival. However, the genetic mechanisms underlying changes in HDL-C during sepsis, and whether the relationship with survival is causative, is largely unknown. Objectives: We hypothesized that variation in genes invo...
Article
Full-text available
Background: Time-restricted feeding regimen (TRF), that is, no food consumption for 14-16 h during the light phase per day, attenuates the fattening traits and metabolic disorders in adults. This study aims to further investigate whether TRF would be protective against similar nutritional challenges in juvenile mice. Methods: Mice in the experim...
Article
Full-text available
The Metabolic Syndrome (MetS) is a complex, multifactorial disorder that develops slowly over time presenting itself with large differences among MetS patients. We applied a systems biology approach to describe and predict the onset and progressive development of MetS, in a study that combined in vivo and in silico models. A new data-driven, physio...
Data
Detailed model description of MINGLeD. (PDF)
Data
Predicted metabolite pools and flux trajectories. Panels a-b display the dynamics in metabolite pools over time and panels e-t display the corresponding flux trajectories. We selected the n = 100 best trajectories (top 10% based on WSSE). The 10% range around the median trajectory is depicted by the shaded area and the median trajectory for each mo...
Article
Full-text available
Background and aims: We recently showed that plasma cholesteryl ester transfer protein (CETP) is mainly derived from VSIG4-positive Kupffer cells. Activation of these cells by the bacterial endotoxin lipopolysaccharide (LPS) strongly decreases CETP expression. As Kupffer cell activation plays a detrimental role in the progression of non-alcoholic...
Article
Full-text available
Epidemiological studies have indicated that rural living might be protective against type 2 diabetes development. We compared the metabolic profile and response to a short-term high-fat high-calorie diet (HFD) of men with the same genetic background living in an urban and rural area of Indonesia. First, we recruited 154 Floresian male subjects (18–...
Article
We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO...
Data
Table S1. Primers Sequences Use for RT‐Qpcr Figure S1. CETP staining in mouse and human livers. Representative picures of IHC staining of CETP protein in liver sections of (A) non‐CETP transgenic mice (APOE*3‐Leiden mice), (B) APOE*3‐Leiden.CETP transgenic mice, and (C) a healthy human donor. Figure S2. LPS acutely increases hepatic Lbp expressio...
Article
Full-text available
Background: Lipopolysaccharide (LPS) decreases hepatic CETP (cholesteryl ester transfer protein) expression albeit that the underlying mechanism is disputed. We recently showed that plasma CETP is mainly derived from Kupffer cells (KCs). In this study, we investigated the role of KC subsets in the mechanism by which LPS reduces CETP expression. M...
Article
Full-text available
Objective Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate. Design Acute effects of butyrate on appetite and its m...
Data
Figure S1. Food intake of E3L.CETP – mice on HFCD diet through time. Figure S2. Liver weight correlates with body weight (ρ = 0.9, P > 0.001). Figure S3. Tracer kinetics of male E3L.CETP mice that were used to measure endogenous glucose production: Mean residence time (A), Bioavailibility (B), AUC (C), apparent volume of distribution (D), metabol...
Data
Data S1. The R‐code to reproduce the gene expression analysis.
Data
Data S2. Matlab code to reproduce the mixed modeling results.
Data
Data S3. Summary of results from gene expression analysis.
Data
Table S1. Summary of results from the mixed modeling analysis.
Article
Full-text available
Physiological adaptations resulting in the development of the metabolic syndrome in man occur over a time span of several decades. This combined with the prohibitive financial cost and ethical concerns to measure key metabolic parameters repeatedly in subjects for the major part of their life span makes that comprehensive longitudinal human data se...
Article
Background and aims: Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would...
Article
Full-text available
Introduction: Adipose tissue has been postulated to contribute substantially to the serum cholesteryl ester transfer protein (CETP) pool. However, in a recent large cohort study waist circumference was not associated with plasma CETP. The aim of the present study was to further examine associations of accurate measures of body fat and body fat dis...
Article
Obesity and dyslipidemia are important risk factors for the development of cardiovascular disease. Niacin is a potent HDL-cholesterol raising drug and decreases white adipose tissue (WAT) lipolysis temporarily. However, chronic niacin treatment results in insulin resistance of WAT, muscle and liver and normalization of WAT lipolysis. Here, we studi...
Article
In mammals, two types of adipose tissue are present: white and brown. While the main function of white adipose tissue (WAT) is the storage of fat, brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1. Interestingly, BAT volume and activity are lower in obese subjects, suggesting that BAT impo...
Article
The GLP-1 receptor agonist exendin-4 (ex-4) improves glucose intolerance and is currently being used in the treatment of type 2 diabetes mellitus.
Article
Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to LDL and high CETP activity results in an atherogenic lipid phenotype. Thus, inhibiting CETP is a target for dyslipidemia treatment. However, the true origin of CETP in humans is uncertain. We aimed to elucidate the cellular origin of CETP and the relative contributio...