Review
Nutrition & Dietetics
Frans Stellaard
Summary: Dietary cholesterol plays a significant role in the endogenous cholesterol pool and affects the serum concentration of total cholesterol, particularly LDL cholesterol. Maintaining a balance in hepatic cholesterol metabolism is crucial for preventing the risk of atherosclerosis and cardiovascular diseases.
Review
Nutrition & Dietetics
Tess Yntema, Debby P. Y. Koonen, Folkert Kuipers
Summary: Despite advancements in prevention and treatment, cardiovascular disease (CVD) remains the leading cause of death worldwide. Recent studies have highlighted the potential role of non-traditional factors, such as the gut microbiota and its metabolites, in CVD. Specifically, disturbances in the gut microbiota and altered bile acid metabolism have been associated with CVD development. Bile acids, apart from their role in lipid absorption and metabolism, have been found to act as signaling molecules and modulate cardiometabolic pathways, making them potential therapeutic targets in CVD.
Article
Pharmacology & Pharmacy
Silke Matysik, Sabrina Krautbauer, Gerhard Liebisch, Hans-Frieder Schott, Louise Kjolbaek, Arne Astrup, Francois Blachier, Martin Beaumont, Max Nieuwdorp, Annick Hartstra, Simone Rampelli, Uberto Pagotto, Patricia Iozzo
Summary: This study quantified the concentrations of faecal sterol species, bile acids, and short-chain fatty acids in 165 study participants. Participants were classified as low or high converters based on their coprostanol/cholesterol ratio, with low converters excreting more straight-chain fatty acids and bile acids. Concentration ranges of 16 faecal metabolites were provided as reference values, showing significant differences in faecal metabolites between high and low sterol converter groups.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Jin-Yue Yang, Tian-Tian Zhang, Zhu-Lin Yu, Xiao-Yue Li, Ying-Cai Zhao, Xiang-Zhao Mao, Yu-Ming Wang, Chang-Hu Xue
Summary: In this study, phosphatidylglucose (PG) was prepared through enzymatic modification of phosphatidylcholine (PC), and its effects on atherosclerosis in ApoE(-/-) mice as well as its dose-response relationship were investigated. The results showed that dietary PG significantly decreased atherosclerotic lesion area in a dose-dependent manner. Furthermore, PG intake decreased cholesterol levels and increased bile acid synthesis, leading to an alleviation of atherosclerosis.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Review
Nutrition & Dietetics
Malgorzata Sidorkiewicz
Summary: The maintenance of cholesterol homeostasis involves complicated processes such as regulation of cholesterol synthesis, dietary uptake, and bile acid synthesis and excretion. Reverse cholesterol transport, mediated by high-density lipoproteins, plays a vital role in transferring cholesterol from non-hepatic cells to the liver for excretion. MicroRNA-33 has been identified as a key regulator of cholesterol homeostasis, impacting both cellular cholesterol efflux and bile metabolism in the liver. Understanding these mechanisms could lead to new perspectives in microRNA-targeted treatment for cholesterol imbalance.
Article
Cardiac & Cardiovascular Systems
Prakriti Gaba, Michelle L. O'Donoghue, Jeong-Gun Park, Stephen D. Wiviott, Dan Atar, Julia F. Kuder, KyungAh Im, Sabina A. Murphy, Gaetano M. De Ferrari, Zbigniew A. Gaciong, Kalman Toth, Ioanna Gouni-Berthold, Jose Lopez-Miranda, Francois Schiele, Francois Mach, Jose H. Flores-Arredondo, J. Antonio G. Lopez, Mary Elliott-Davey, Bei Wang, Maria Laura Monsalvo, Siddique Abbasi, Robert P. Giugliano, Marc S. Sabatine
Summary: This study found that long-term achievement of lower LDL-C levels (below 20 mg/dL) in patients with atherosclerotic cardiovascular disease was associated with a lower risk of cardiovascular events without significant safety concerns.
Review
Chemistry, Medicinal
Saba Soltani, Motahareh Boozari, Arrigo F. G. Cicero, Tannaz Jamialahmadi, Amirhossein Sahebkar
Summary: HDL plays a crucial role in cardiovascular diseases, while phytochemicals have the potential to enhance cholesterol efflux. Current research mostly focuses on preclinical studies, indicating a need for more clinical research to develop novel clinical applications.
PHYTOTHERAPY RESEARCH
(2021)
Article
Chemistry, Applied
Purnima Gunness, Honglei Zhai, Barbara A. Williams, Dagong Zhang, Michael J. Gidley
Summary: The study found that pectin can reduce plasma cholesterol and triglyceride levels, increase total bile acid levels, and have different effects on intestinal cholesterol compared to mango; pectin has prebiotic properties and promotes the increase of therapeutic bile acid ursodesoxycholic acid (UDCA).
FOOD HYDROCOLLOIDS
(2021)
Article
Hematology
Jiahuan Chen, Huanyu Zhang, Linquan Li, Xinwei Zhang, Dazhong Zhao, Lingyu Wang, Jiaqi Wang, Ping Yang, Huan Sun, Kun Liu, Weiwei Chen, Lin Li, Feng Lin, Zhanjun Li, Y. Eugene Chen, Jifeng Zhang, Daxin Pang, Hongsheng Ouyang, Yuquan He, Jianglin Fan, Xiaochun Tang
Summary: In this study, Lp-PLA(2) knockout rabbits were generated using the CRISPR/Cas9 system to investigate the role of Lp-PLA(2) in blood lipid regulation and atherosclerosis. The results showed that Lp-PLA(2) deficiency reduced plasma lipid levels and protected against cholesterol-induced atherosclerosis in rabbits. Furthermore, Lp-PLA(2) deficiency impaired cholesterol biosynthesis and inhibited the adhesion between monocytes and endothelial cells.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Review
Hematology
Christian M. Madsen, Anette Varbo, Borge G. Nordestgaard
Summary: Recent studies have suggested that extremely high levels of HDL cholesterol are associated with increased mortality, indicating that HDL may have harmful effects in some instances. Furthermore, observational and genetic studies have shown that HDL might be linked to the development of major noncardiovascular diseases.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Chiara Reggio, Erika Palmisano, Umberto Tecchiati, Alessandro Ravelli, Roberta F. F. Bergamaschi, Paola Salzani, Cristiano Putzolu, Sara Casati, Marica Orioli
Summary: The aim of this research is to identify mammalian species through faecal sediments in both modern and ancient environments, which is of interest to archaeologists, forensic scientists, and ecologists. The researchers have developed an optimized gas chromatography-mass spectrometry (GC-MS) method with a time-saving sample preparation protocol to analyze faecal biomarkers in soil samples from an archaeological site in Italy. By comparing these biomarker findings with new studies on faunal materials, the researchers can gain insights into the animal species farmed in the area and the management of breeding. This investigation, along with archaeozoological and archaeobotanical analyses, contributes to our understanding of how ancient communities utilized natural resources and their impact on the landscape.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Ioannis Evangelakos, Anastasia Kuhl, Miriam Baguhl, Christian Schlein, Clara John, Julia K. Rohde, Markus Heine, Joerg Heeren, Anna Worthmann
Summary: Brown adipose tissue (BAT) is an attractive therapeutic target for cardio metabolic diseases due to its heat-producing function and ability to lower hyperlipidemia. The synthesis of bile acids (BA) and activation of thermogenesis in BAT are important for systemic lipid metabolism. The study reveals that Cyp7b1 plays a crucial role in BAT function and lipid clearance.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Shifa Jebari-Benslaiman, Kepa B. Uribe, Asier Benito-Vicente, Unai Galicia-Garcia, Asier Larrea-Sebal, Izortze Santin, Iraide Alloza, Koen Vandenbroeck, Helena Ostolaza, Cesar Martin
Summary: A therapeutic strategy based on apoA-I nanoparticles has been developed to improve the treatment of atherosclerosis. The strategy involves a two-step administration to induce gene overexpression and promote cholesterol efflux. Experimental results indicate that this approach can efficiently target atherosclerotic lesions and improve prognosis.
Article
Biochemistry & Molecular Biology
Na Zhan, Boyang Wang, Nikita Martens, Yankai Liu, Shangge Zhao, Gardi Voortman, Jeroen Van Rooij, Frank Leijten, Tim Vanmierlo, Folkert Kuipers, Johan W. Jonker, Vincent W. Bloks, Dieter Luetjohann, Marcella Palumbo, Francesca Zimetti, Maria Pia Adorni, Hongbing Liu, Monique T. Mulder
Summary: The study identified five novel LXR-activating 24-oxidized sterols with potential therapeutic applications in neurodegenerative and cardiovascular diseases. These compounds demonstrated high potency for LXR alpha/beta activation and induced the expression of LXR-target genes involved in cellular cholesterol turnover. They also enhanced cholesterol efflux and upregulated the production of endogenous LXR agonists. Overall, these findings suggest the potential of developing compounds targeting LXR for the treatment of lipid-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Yu Fu, Han Feng, Xue Ding, Qing-Hai Meng, Shu-Rui Zhang, Jun Li, Ying Chao, Ting-Ting Ji, Yun-Hui Bi, Wei-Wei Zhang, Qi Chen, Yu-Han Zhang, You-Long Feng, Hui-Min Bian
Summary: AB23A may prevent postmenopausal atherosclerosis by regulating hepatic farnesoid X receptor, increasing bile acid and cholesterol excretion, and reducing plasma cholesterol levels, providing a potential therapeutic approach.
Article
Multidisciplinary Sciences
Maaike Blankestijn, Vincent W. Bloks, Dicky Struik, Nicolette Huijkman, Niels Kloosterhuis, Justina C. Wolters, Ronald J. A. Wanders, Frederic M. Vaz, Markus Islinger, Folkert Kuipers, Bart van de Sluis, Albert K. Groen, Henkjan J. Verkade, Johan W. Jonker
Summary: The study of a Pxmp4 knockout mouse model suggests that PXMP4 is not critical for overall peroxisome function but may have a role in the metabolism of (ether)lipids.
SCIENTIFIC REPORTS
(2022)
Review
Medicine, General & Internal
Boyan Zhang, Folkert Kuipers, Jan Freark de Boer, Jan Albert Kuivenhoven
Summary: This review evaluates the potential of new drugs targeting bile acid metabolism in the treatment of cholestatic liver diseases, NAFLD, and NASH. The review also explores the impact of changes in bile acid metabolism on plasma cholesterol, triglycerides, and cardiovascular outcomes. The findings highlight the need for further research on the interactions between bile acid and lipid and lipoprotein metabolism.
JOURNAL OF CLINICAL MEDICINE
(2022)
Letter
Gastroenterology & Hepatology
Onne A. H. O. Ronda, Vincent W. Bloks, Jan-Freark De Boer, Folkert Kuipers, Henkjan J. Verkade
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Pediatrics
Hilde D. de Vries, Anna Palmiotti, Rumei Li, Milaine Hovingh, Niels L. Mulder, Martijn Koehorst, Vincent W. Bloks, Tim van Zutphen, Folkert Kuipers, Jan Freark de Boer
Summary: Perinatal exposure to UDCA can prevent neonatal cholestasis in Cyp2c70(-/-) mice, but has no long-lasting effects on liver pathophysiology.
PEDIATRIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
J. Yang, H. D. de Vries, A. Mayeuf-Louchart, J. H. Stroeve, V. W. Bloks, M. Koehorst, H. Duez, B. Staels, F. Kuipers, T. van Zutphen
Summary: Bile acids, acting through the G-protein-coupled receptor TGR5, play a role in energy homeostasis in mice and humans. However, the role of the nuclear bile acid receptor FXR in brown adipose tissue (BAT) has been unclear. This study demonstrates that moderate adipose tissue-specific overexpression of FXR in mice leads to whitening of BAT, with changes in lipid droplets, collagen deposition, and gene expression. These findings suggest that bile acid signalling via FXR is involved in BAT function during tissue development, and may oppose the thermogenic effects mediated by TGR5.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Biochemistry & Molecular Biology
Na Zhan, Boyang Wang, Nikita Martens, Yankai Liu, Shangge Zhao, Gardi Voortman, Jeroen Van Rooij, Frank Leijten, Tim Vanmierlo, Folkert Kuipers, Johan W. Jonker, Vincent W. Bloks, Dieter Luetjohann, Marcella Palumbo, Francesca Zimetti, Maria Pia Adorni, Hongbing Liu, Monique T. Mulder
Summary: The study identified five novel LXR-activating 24-oxidized sterols with potential therapeutic applications in neurodegenerative and cardiovascular diseases. These compounds demonstrated high potency for LXR alpha/beta activation and induced the expression of LXR-target genes involved in cellular cholesterol turnover. They also enhanced cholesterol efflux and upregulated the production of endogenous LXR agonists. Overall, these findings suggest the potential of developing compounds targeting LXR for the treatment of lipid-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Arianna Marino, Laura Butruille, Denis A. Mogilenko, Arielle C. Nzoussi Loubota, Oscar Chavez-Talavera, Emilie Dorchies, Emmanuelle Vallez, Joel Haas, Bruno Derudas, Antonino Bongiovanni, Meryem Tardivel, Folkert Kuipers, Philippe Lefebvre, Sophie Lestavel, Anne Tailleux, David Dombrowicz, Sandrine Caron, Bart Staels
Summary: This study reveals the regulatory role of FXR in adipose tissue function in obese rats, improving glucose metabolism and systemic oxidative stress by inhibiting inflammatory responses and enhancing insulin sensitivity. Transcriptomic analysis identified the Gsta4 gene as the most upregulated gene in Ad-FXR-/- mouse adipocytes.
MOLECULAR METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Jiufang Yang, Theo H. van Dijk, Martijn Koehorst, Rick Havinga, Jan Freark de Boer, Folkert Kuipers, Tim van Zutphen
Summary: Bile acids are involved in the absorption of dietary lipids and serve as signaling molecules for metabolic homeostasis. FXR, a nuclear receptor responsive to bile acids, has been implicated in bile acid metabolism and lipid and glucose homeostasis. However, this study found that intestinal FXR does not play a role in glucose absorption, but does affect small intestinal surface area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Nutrition & Dietetics
Tess Yntema, Debby P. Y. Koonen, Folkert Kuipers
Summary: Despite advancements in prevention and treatment, cardiovascular disease (CVD) remains the leading cause of death worldwide. Recent studies have highlighted the potential role of non-traditional factors, such as the gut microbiota and its metabolites, in CVD. Specifically, disturbances in the gut microbiota and altered bile acid metabolism have been associated with CVD development. Bile acids, apart from their role in lipid absorption and metabolism, have been found to act as signaling molecules and modulate cardiometabolic pathways, making them potential therapeutic targets in CVD.
Article
Medicine, Research & Experimental
Esther Verkade, Wenqiang Shen, Milaine Hovingh, Niels L. Mulder, Krisztina de Bruyn, Martijn Koehorst, Hilde D. de Vries, Vincent W. Bloks, Folkert Kuipers, Jan Freark de Boer
Summary: This study suggests that depletion of gut microbiota in Cyp2c70-/- mice aggravates liver pathology by increasing the hydrophobicity of the circulating bile acid pool. Additionally, the impact of antibiotic treatment on Cyp2c70-/- mice differs between genders, with more severe effects observed in female mice.
Article
Medicine, Research & Experimental
Wilhelm Sjoland, Annika Wahlstrom, Kassem Makki, Marc Scholer, Antonio Molinaro, Lisa Olsson, Thomas Uwe Greiner, Robert Caesar, Jan Freark de Boer, Folkert Kuipers, Fredrik Backhed, Hanns-Ulrich Marschall
Summary: Mice with deletion of Cyp2c70 exhibit features of hepatobiliary disease and can serve as a model for studying bile acid interactions in cholestatic liver disease. Germ-free Cyp2c70-/- mice showed reduced neonatal survival, liver fibrosis, and cholangiocyte proliferation. Colonization with a microbiota, particularly from conventionally raised mice, improved the liver phenotype in Cyp2c70-/- mice and was associated with changes in bile acid composition and gut microbiota.
Article
Medicine, Research & Experimental
Enchen Zhou, Xiaoke Ge, Hiroyuki Nakashima, Rumei Li, Hendrik J. P. van der Zande, Cong Liu, Zhuang Li, Christoph Mueller, Franz Bracher, Yassene Mohammed, Jan Freark de Boer, Folkert Kuipers, Bruno Guigas, Christopher K. Glass, Patrick C. N. Rensen, Martin Giera, Yanan Wang
Summary: DHCR24 inhibition prevents the development of NAFLD/NASH without causing hyperlipidemia. SH42, a DHCR24 inhibitor, significantly increases desmosterol levels, reduces hepatic lipid content and steatosis, and decreases plasma fatty acid and cholesteryl ester concentrations. SH42 treatment also decreases liver collagen content and plasma alanine transaminase levels.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Sebastian Hendrix, Jenina Kingma, Roelof Ottenhoff, Masoud Valiloo, Monika Svecla, Lobke F. Zijlstra, Vinay Sachdev, Kristina Kovac, Johannes H. M. Levels, Aldo Jongejan, Jan F. de Boer, Folkert Kuipers, Antoine Rimbert, Giuseppe D. Norata, Anke Loregger, Noam Zelcer
Summary: SPRING is identified as a post-transcriptional regulator of SREBP activation, controlling cholesterol and fatty acid metabolism. Liver-specific knockout of Spring results in attenuated SREBP signaling, decreased plasma cholesterol, and reduced hepatic lipid content in mice. SPRING gene variants are also associated with levels of circulating HDL cholesterol and ApoA1 in humans. This study highlights the importance of SPRING in hepatic SREBP signaling and systemic lipid metabolism in both mice and humans.
NATURE COMMUNICATIONS
(2023)
Article
Nutrition & Dietetics
Nikita Martens, Na Zhan, Gardi Voortman, Frank P. J. Leijten, Connor van Rheenen, Suzanne van Leerdam, Xicheng Geng, Michiel Huybrechts, Hongbing Liu, Johan W. W. Jonker, Folkert Kuipers, Dieter Lutjohann, Tim Vanmierlo, Monique T. T. Mulder
Summary: The nuclear liver X receptors (LXRα/β) and peroxisome proliferator-activated receptors (PPARα/γ) play a role in regulating lipid metabolism and inflammation. The activation of these receptors has neuroprotective effects and may be a potential treatment for neurodegenerative disorders like Alzheimer's Disease (AD). The brown seaweed Sargassum fusiforme contains compounds that activate these receptors and have been shown to prevent disease progression in a mouse model of AD.
Article
Medicine, Research & Experimental
Shiqi Zhong, Raphael Chevre, David Castano Mayan, Maria Corliano, Blake J. Cochran, Kai Ping Sem, Theo H. van Dijk, Jianhe Peng, Liang Juin Tan, Siddesh V. Hartimath, Boominathan Ramasamy, Peter Cheng, Albert K. Groen, Folkert Kuipers, Julian L. Goggi, Chester Drum, Rob M. van Dam, Ru San Tan, Kerry-Anne Rye, Michael R. Hayden, Ching-Yu Cheng, Shaji Chacko, Jason Flannick, Xueling Sim, Hong Chang Tan, Roshni R. Singaraja
Summary: Reduced CYP8B1 activity is associated with increased insulin sensitivity in humans, possibly due to increased skeletal muscle insulin sensitivity caused by increased circulating CDCA.
JOURNAL OF CLINICAL INVESTIGATION
(2022)