Patrick C.N. Rensen

Patrick C.N. Rensen
Leiden University Medical Centre | LUMC · Department of Endocrinology and General Internal Medicine

Prof. dr.

About

506
Publications
37,784
Reads
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10,836
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Introduction
Prof. dr. PCN Rensen is Head of the Endocrinology Research Lab at the LUMC. He obtained his MSc and PhD degrees cum laude and was appointed as Full Prof in 2012. He was awarded personal grants by LUMC, NWO (VIDI) and Heart Foundation (EI). He is President of the European Lipoprotein Club (2018-2023). Current grant support includes Heart Foundation, Diabetes Foundation, EFSD and CSC. His research focuses on the role of brown fat in lipid metabolism and its implications for diabetes and atherosclerosis.
Research Experience
July 2001 - present
Leiden University Medical Centre
Position
  • Professor, Head of Endocrinology Research Lab

Publications

Publications (506)
Article
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Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a re...
Article
USF1 (upstream stimulatory factor 1) is a transcription factor associated with familial combined hyperlipidemia and coronary artery disease in humans. However, whether USF1 is beneficial or detrimental to cardiometabolic health has not been addressed. By inactivating USF1 in mice, we demonstrate protection against diet-induced dyslipidemia, obesity...
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Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases bod...
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Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic receptor stimulation protects from atherosclerosis in...
Article
Individuals of south Asian origin have a very high risk of developing type 2 diabetes compared with white Caucasians. We aimed to assess volume and activity of brown adipose tissue (BAT), which is thought to have a role in energy metabolism by combusting fatty acids and glucose to produce heat and might contribute to the difference in incidence of...
Article
AimsData on the effect of liraglutide on glycemic endpoints in people with T2DM using multiple daily insulin injections (MDI) are scarce, especially in the context of ethnicity. Methods This is a secondary analysis of the placebo-controlled randomized clinical “MAGNA VICTORIA” trials in Western European (WE) and South Asian (SA) people with T2DM. P...
Article
Microglia are brain immune cells responsible for immune surveillance. Microglial activation is, however, closely associated with neuroinflammation, neurodegeneration, and obesity. Therefore, it is critical that microglial immune response appropriately adapts to different stressors. The circadian clock controls the cellular process that involves the...
Article
Circadian disruption induced by shift work is robustly associated with obesity, diabetes, and cardiovascular disease in humans. Less well-known are the mechanisms underlying these associations, and the effectiveness of strategies to reduce cardiometabolic risk in the shift work population. In this review, the different ways in which shift work can...
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,...
Preprint
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Type II diabetes mellitus (T2DM) has reached endemic levels and comprises a substantial burden to the patient and the society. Along with lifestyle factors, a number of genetic loci predisposing to T2DM have been suggested including SORCS1 that encodes a type-1 transmembrane receptor. Here we establish SorCS1 as a high-affinity binding partner for...
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Background & Aims: While fibrosis stage predicts liver-associated mortality, cardiovascular disease (CVD) is still the major overall cause of mortality in patients with NASH. Novel NASH drugs should thus ideally reduce both liver fibrosis and CVD. Icosabutate is a semi-synthetic, liver-targeted eicosapentaenoic acid (EPA) derivative in clinical dev...
Article
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...
Preprint
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Background: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic trai...
Article
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
Full-text available
Background & Aims Whilst fibrosis stage predicts liver‐associated mortality, cardiovascular disease (CVD) is still the major overall cause of mortality in patients with NASH. Novel NASH drugs should thus ideally reduce both liver fibrosis and CVD. Icosabutate is a semi‐synthetic, liver‐targeted eicosapentaenoic acid (EPA) derivative in clinical dev...
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Careful design of experiments using living organisms (e.g. mice) is of critical importance from both an ethical and a scientific standpoint. Randomization should, whenever possible, be an integral part of such experimental design to reduce bias thereby increasing its reliability and reproducibility. To keep the sample size as low as possible, one m...
Article
Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β3-adrenergic receptor (β3-AR), the adrenergic receptor believed to mediate BAT thermogenesis, have historically performed poorly in human clinical trials. Here we report that,...
Article
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Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for b...
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Background and aims Outdoor temperature and bright sunlight may directly and/or indirectly modulate systemic metabolism. We assessed the associations between outdoor temperature and bright sunlight duration with metabolomics. Methods and Results Cross-sectional analyses were undertaken in non-diabetic individuals from the Oxford BioBank (OBB; N=6,...
Article
Background: The increase in serum triglyceride (TG) concentrations in response to a meal is considered a risk factor for cardiovascular disease. We aimed to elucidate the genetics of the postprandial TG response through genome-wide association studies (GWAS). Methods: Participants of the NEO (Netherlands Epidemiology of Obesity) study (n=5630) c...
Article
Aims: To compare the effects of cold exposure and the β3-adrenergic receptor agonist mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT) activity in South Asians versus Europids. Material and methods: Ten lean Dutch South Asian (age 18-30 years; BMI 18-25 kg/m2 ) and ten age- and BMI-matched Europid men participated in...
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Objective Exercise has been shown to improve cardiometabolic health, yet neither the molecular connection nor the effects of exercise timing have been elucidated. The aim of this study was to investigate whether ad libitum or time‐restricted mild exercise reduces atherosclerosis development in atherosclerosis‐prone dyslipidemic APOE*3‐Leiden.CETP m...
Article
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Exercise is a valuable tool in the prevention and treatment of cardiometabolic diseases like obesity and type 2 diabetes. Interestingly, endocannabinoids (eCBs), involved in a large range of physiological processes, are elevated with both obesity and acute exercise. In this review we outline this paradox overlap in the context of metabolic health a...
Article
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Narcolepsy type 1 is a neurological sleep-wake disorder caused by the destruction of orexin (hypocretin)-producing neurons. These neurons are particularly located in the lateral hypothalamus and have widespread projections throughout the brain, where they are involved, e.g., in the regulation of the sleep-wake cycle and appetite. Interestingly, a h...
Preprint
Introduction: Carriers of the APOE ϵ4 genotype have an increased risk for developing coronary artery disease (CAD), but there is preliminary evidence that lifestyle factors interact with APOE genotype on CAD risk. Here, we assessed the interactions of physical activity, oily fish intake and polyunsaturated fatty acid (PUFA) intake with APOE genotyp...
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
Aims/hypothesis: Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, pos...
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Aim: Magnetic resonance imaging (MRI) is increasingly being used to evaluate brown adipose tissue (BAT) function. Reports on the extent and direction of cold-induced changes in MRI fat fraction and estimated BAT volume vary between studies. Here, we aimed to explore the effect of different fat fraction threshold ranges on outcomes measured by MRI....
Article
Aims: Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk for cardiovascular disease (CVD) linked to atherogenic dyslipidemia and postprandial hyperlipidemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C)...
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Aims/hypothesis The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus. Methods This study is a pre-specified subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA...
Article
Background C-type lectin receptors, including Dectin-2, are pattern recognition receptors on monocytes and macrophages that mainly recognize sugars and sugar-like structures present on fungi. Activation of C-type lectin receptors induces downstream CARD9 signalling, leading to the production of cytokines. We hypothesized that under hyperglycaemic c...
Article
Background and aims: Several studies have shown that glucagon-like peptide-1 (GLP-1) analogues can affect resting energy expenditure, and preclinical studies suggest that they may activate brown adipose tissue (BAT). The aim of the present study was to investigate the effect of treatment with liraglutide on energy metabolism and BAT fat fraction i...
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Background: The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide may be beneficial in the regression of diabetic cardiomyopathy. South Asian ethnic groups in particular are at risk of developing type 2 diabetes. Purpose: To assess the effects of liraglutide on left ventricular (LV) diastolic and systolic function in South Asian type...
Article
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The past decade, it has become evident that circadian rhythms within metabolically active tissues are very important for physical health. However, although shift work has also been associated with an increased risk of fractures, circadian rhythmicity has not yet been extensively studied in bone. Here, we investigated which genes are rhythmically ex...
Article
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Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery +...
Article
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Background: South Asians generally have an unfavourable metabolic phenotype compared with white Caucasians, including central obesity and insulin resistance. The Wnt protein family interacts with insulin signaling, and impaired Wnt signaling is associated with adiposity and type 2 diabetes mellitus. We aimed to investigate Wnt signaling in relatio...
Preprint
Full-text available
Context: Outdoor temperature and bright sunlight may directly and/or indirectly modulate systemic metabolism. Objective: We assessed the associations between outdoor temperature and bright sunlight duration with metabolomics. Design: meta-analysis of two cross-sectional studies. Setting: Two population-based European cohort studies. Patients or oth...
Article
Full-text available
Disruption of circadian rhythm by means of shift work has been associated with cardiovascular disease in humans. However, causality and underlying mechanisms have not yet been established. In this study, we exposed hyperlipidemic APOE*3‐Leiden.CETP mice to either regular light‐dark cycles, weekly 6 h phase advances or delays, or weekly alternating‐...
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
Targeting metabolism through bioactive key metabolites is an upcoming future therapeutic strategy. We questioned how modifying intracellular lipid metabolism could be a possible means for alleviating inflammation. Using a recently developed chemical probe (SH42), we inhibited distal cholesterol biosynthesis through selective inhibition of Δ ²⁴ -deh...
Article
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Background: South Asians are more prone to develop atherosclerotic cardiovascular disease (ASCVD) compared with white Caucasians, which is not fully explained by classical risk factors. We recently reported that the presence of aggregation-prone low-density lipoprotein (LDL) in the circulation is associated with increased ASCVD mortality. Objecti...
Article
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Angiopoietin-like proteins (ANGPTLs) regulate triglyceride (TG)-rich lipoprotein distribution via inhibiting TG hydrolysis by lipoprotein lipase in metabolic tissues. Brown adipose tissue combusts TG-derived fatty acids to enhance thermogenesis during cold exposure. It has been shown that cold exposure regulates ANGPTL4, but its effects on ANGPTL3...
Article
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Objectives Short sleep duration and sleep disturbances have been related to obesity and metabolic disruption. However, the behavioural and physiological mechanisms linking sleep and alterations in energy balance and metabolism are incompletely understood. In rodents, sleep regulation is closely related to appropriate brown adipose tissue (BAT) ther...
Article
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The present study examines whether the daily rhythm of distal skin temperature (DST) is associated with brown adipose tissue (BAT) metabolism as determined by 18 F-fluorodeoxyglucose (18 F-FDG) uptake in young adults. Using a wireless thermometer (iButton) worn on the nondominant wrist, DST was measured in 77 subjects (26% male; age 22 ± 2 years; b...
Article
Brown adipose tissue (BAT) catabolizes glucose and fatty acids to produce heat and thereby contributes to energy expenditure. Long-term high fat diet (HFD) feeding results in so-called 'whitening' of BAT characterized by increased lipid deposition, mitochondrial dysfunction and reduced fat oxidation. The aim of the current study was to unravel the...
Article
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Scope: Akkermansia muciniphila (A. muciniphila) is an intestinal commensal with anti-inflammatory properties both in the intestine and other organs. We aimed to investigate the effects of oral administration of A. muciniphila on lipid metabolism, immunity and cuff-induced neointima formation in hyperlipidemic APOE*3-Leiden (E3L).CETP mice. Method...
Article
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Brown adipose tissue (BAT) is a potential target to treat cardiometabolic disorders because of its capacity to combust glucose and fatty acids for thermoregulation. Its cellular and molecular investigation in humans is hampered by the limited availability of cell material and the heterogeneity of BAT between and within individuals. In this study, m...
Article
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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
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Background: South Asians have a high risk to develop type 2 diabetes, which may be related to substantial ectopic fat deposition. Since glucagon-like peptide-1 analogues can reduce ectopic fat accumulation, the aim of the present study was to assess the effect of treatment with liraglutide for 26 weeks on ectopic fat deposition and HbA1c in South...
Article
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Bile acids play a major role in the regulation of lipid and energy metabolism. Here we propose the hepatic bile acid uptake transporter Na+ taurocholate co-transporting polypeptide (NTCP) as a target to prolong postprandial bile acid elevations in plasma. Reducing hepatic clearance of bile acids from plasma by genetic deletion of NTCP moderately in...
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Purpose Nowadays, 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography (PET)/X-ray computed tomography (CT) is considered the best available technique to in vivo determination of human BAT volume. The most used Hounsfield unit (HU) threshold for BAT quantification is from – 250 to − 50 HU. Therefore, the main objective of the pre...