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| Open AccessAtherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation
Accumulation of lipid-laden macrophages in the arterial wall is a critical step in atherosclerosis. Here, the authors show that downregulation of Zeb1 in macrophages promotes lipid accumulation and atherosclerotic plaque formation while its restoration with macrophage-targeted nanoparticles reverses these effects.
- M. C. Martinez-Campanario
- , Marlies Cortés
- & Antonio Postigo
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Article
| Open AccessHepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans
Hendrix et al show that absence of hepatic Spring dramatically lowers levels of lipids in the liver and plasma in mice, and protects from development of diet-induced steatosis. In line, genetic variation in SPRING is associated with lipid levels in humans.
- Sebastian Hendrix
- , Jenina Kingma
- & Noam Zelcer
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Article
| Open AccessIntestine-enriched apolipoprotein b orthologs are required for stem cell progeny differentiation and regeneration in planarians
Lipid metabolism regulates stem cell states and differentiation. Here, the authors demonstrate a requirement in planarians for Apolipoprotein B-mediated neutral lipid transport from intestinal stores to stem cells and their progeny during differentiation and whole-body regeneration.
- Lily L. Wong
- , Christina G. Bruxvoort
- & David J. Forsthoefel
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Article
| Open AccessStructural basis of the membrane intramolecular transacylase reaction responsible for lyso-form lipoprotein synthesis
In Gram-positive bacteria, lipoprotein intramolecular transacylase Lit produces a lipoprotein variant with less immunogenicity. As such, Lit can be viewed as a virulence factor. Here, structural and functional characterization of the enzyme provides insight into its catalytic mechanism, setting the stage for future studies of Lit as a target for new antibiotics.
- Samir Olatunji
- , Katherine Bowen
- & Martin Caffrey
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Article
| Open AccessMembrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis
Elevated plasma LDL cholesterol levels increase the risk of atherosclerotic cardiovascular disease. Here, the authors show that inhibition of MT1-MMP reduces plasma LDL cholesterol levels and the risk of atherosclerosis, indicating the potential of MT1-MMP inhibition as a lipid-lowering therapy.
- Adekunle Alabi
- , Xiao-Dan Xia
- & Da-Wei Zhang
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Article
| Open AccessThe lipoprotein Pal stabilises the bacterial outer membrane during constriction by a mobilisation-and-capture mechanism
The lipoprotein Pal participates in the coordination of outer-membrane constriction with septation in Gram-negative bacteria. Here, the authors show that this coordination is mediated by active mobilisation-and-capture of Pal at division septa by the Tol system.
- Joanna Szczepaniak
- , Peter Holmes
- & Colin Kleanthous
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Article
| Open AccessRelationship between gut microbiota and circulating metabolites in population-based cohorts
Here, the authors provide an in-depth study of the metabolome in two large population-based prospective cohorts and identify 32 microbial traits associated with various metabolic biomarkers and specific lipoprotein subfractions, providing insights into the role of microbiota in influencing host lipid levels.
- Dina Vojinovic
- , Djawad Radjabzadeh
- & Cornelia M. van Duijn
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| Open AccessProtein determinants of dissemination and host specificity of metallo-β-lactamases
Metallo-β-lactamases (MBLs) confer resistance to carbapenem antibiotics. Here, López et al. show that the host range of MBLs depends on the efficiency of MBL signal peptide processing and secretion into outer membrane vesicles, which affects bacterial fitness.
- Carolina López
- , Juan A. Ayala
- & Alejandro J. Vila
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Article
| Open AccessBrain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis
Obesity is associated with leptin resistance and rising blood leptin levels while central leptin exposure may be limited. Here, the authors show that brain leptin infusion reduces hepatic lipid content in rats by increasing hepatic VLDL secretion and lowering liver de novo lipogenesis via a vagal mechanism.
- Martina Theresa Hackl
- , Clemens Fürnsinn
- & Thomas Scherer
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Article
| Open AccessA giant amphipathic helix from a perilipin that is adapted for coating lipid droplets
Lipid droplets are cellular organelles important for cellular homeostasis and their disruption has been implicated in many diseases. Here the authors use a large amphipathic helix from perilipin 4 to uncover parameters important for specific lipid droplet targeting and stabilization of the oil core.
- Alenka Čopič
- , Sandra Antoine-Bally
- & Catherine L. Jackson
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Article
| Open AccessLipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply
Lipoprotein lipase (LPL) hydrolyzes triglycerides to supply free fatty acids (FFAs) to muscle for energy and adipocytes for storage. Here, the authors demonstrate that Lpl and its product, the FFA docosahexaenoic acid (DHA) are required for haematopoietic stem progenitor cell expansion during zebrafish embryogenesis.
- Chao Liu
- , Tianxu Han
- & Yury I. Miller
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Article
| Open AccessThermogenic adipocytes promote HDL turnover and reverse cholesterol transport
Activation of brown adipose tissue (BAT) reduces the development of atherosclerosis in animal models. Here the authors show that BAT activation also increases reverse cholesterol transport and turnover of high-density lipoprotein, which likely contributes to the anti-atherosclerotic effect of BAT activation.
- Alexander Bartelt
- , Clara John
- & Joerg Heeren
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| Open AccessThe RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation
RNA-binding proteins (RBP) are an emerging group of post-translational regulators. Here the authors show that the RBP vigilin regulates translation of mRNA encoding for proatherogenic proteins—apoB, apoC-III and fibronectin—representing a potential therapeutic target in cardiovascular diseases.
- Mehrpouya B. Mobin
- , Stefanie Gerstberger
- & Markus Stoffel
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Article
| Open AccessCCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL
Low density lipoprotein receptor (LDLR) is crucial for cholesterol homeostasis. Here, the authors show that components of the CCC-protein complex, CCDC22 and COMMD1, facilitate the endosomal sorting of LDLR and that mutations in these genes cause hypercholesterolemia in dogs and mice, providing new insights into regulation of cholesterol homeostasis.
- Paulina Bartuzi
- , Daniel D. Billadeau
- & Bart van de Sluis
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Article
| Open AccessD25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile
Decrease in Apolipoprotein C-III (ApoC-III) yields a cardioprotective lipoprotein profile. Here, Valleix et al.reveal a novel ApoC-III variant conferring low plasma ApoC-III concentration and cardioprotection despite renal insufficiency, and, unexpectedly, causing dominant hereditary systemic amyloidosis due to its fibrillogenic nature.
- Sophie Valleix
- , Guglielmo Verona
- & Vittorio Bellotti
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A fatty acid-dependent hypothalamic–DVC neurocircuitry that regulates hepatic secretion of triglyceride-rich lipoproteins
The brain has a central role in the regulation of organismal energy homeostasis. Here the authors show that neurons in the mediobasal hypothalamus respond to fatty acids by generating neuronal signals, relayed to the liver viavagal nerves that mediate secretion of very-low-density lipoproteins.
- Jessica T. Y. Yue
- , Mona A. Abraham
- & Tony K. T. Lam