Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure

Mao, Hong; Szafranska, Karolina; Kruse, Larissa; Holte, Christopher; Wolfson, Deanna L.; Ahluwalia, Balpreet Singh; Whitchurch, Cynthia B.; Cole, Louise; Lockwood, Glen P.; Diekmann, Robin; Le Couteur, David; Cogger, Victoria C.; McCourt, Peter A. G.

doi:10.1038/s41598-023-40227-0

Cited by 4 publications

(1 citation statement)

References 64 publications

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“…Furthermore, LSECs incubated under 20% oxygen tension produced more lactate but did not consume more glucose. Since the publication of these results, various research groups have used conditions of 5% [46,78] or atmospheric [20,79,80] oxygen tension in their studies of LSEC biology.…”

Section: Different Oxygen Tensions In Studies In Primary Lsecsmentioning

confidence: 99%

Liver sinusoidal endothelial cells rely on oxidative phosphorylation but avoid processing long-chain fatty acids in their mitochondria

Kaczara,

Czyzynska-Cichon,

Kus

et al. 2024

Cell Mol Biol Lett

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Background It is generally accepted that endothelial cells (ECs), primarily rely on glycolysis for ATP production, despite having functional mitochondria. However, it is also known that ECs are heterogeneous, and their phenotypic features depend on the vascular bed. Emerging evidence suggests that liver sinusoidal ECs (LSECs), located in the metabolically rich environment of the liver, show high metabolic plasticity. However, the substrate preference for energy metabolism in LSECs remains unclear. Methods Investigations were conducted in primary murine LSECs in vitro using the Seahorse XF technique for functional bioenergetic assays, untargeted mass spectrometry-based proteomics to analyse the LSEC proteome involved in energy metabolism pathways, liquid chromatography-tandem mass spectrometry-based analysis of acyl-carnitine species and Raman spectroscopy imaging to track intracellular palmitic acid. Results This study comprehensively characterized the energy metabolism of LSECs, which were found to depend on oxidative phosphorylation, efficiently fuelled by glucose-derived pyruvate, short- and medium-chain fatty acids and glutamine. Furthermore, despite its high availability, palmitic acid was not directly oxidized in LSEC mitochondria, as evidenced by the acylcarnitine profile and etomoxir’s lack of effect on oxygen consumption. However, together with l-carnitine, palmitic acid supported mitochondrial respiration, which is compatible with the chain-shortening role of peroxisomal β-oxidation of long-chain fatty acids before further degradation and energy generation in mitochondria. Conclusions LSECs show a unique bioenergetic profile of highly metabolically plastic ECs adapted to the liver environment. The functional reliance of LSECs on oxidative phosphorylation, which is not a typical feature of ECs, remains to be determined.

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Section: Different Oxygen Tensions In Studies In Primary Lsecsmentioning

confidence: 99%

Liver sinusoidal endothelial cells rely on oxidative phosphorylation but avoid processing long-chain fatty acids in their mitochondria

Kaczara,

Czyzynska-Cichon,

Kus

et al. 2024

Cell Mol Biol Lett

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Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation

Czyzynska-Cichon,

Kotlinowski,

Blacharczyk

et al. 2024

Cell Mol Biol Lett

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Background Liver sinusoidal endothelial cells (LSECs) have transcellular pores, called fenestrations, participating in the bidirectional transport between the vascular system and liver parenchyma. Fenestrated LSECs indicate a healthy phenotype of liver while loss of fenestrations (defenestration) in LSECs is associated with liver pathologies. Methods We introduce a unique model of systemic inflammation triggered by the deletion of Mcpip1 in myeloid leukocytes (Mcpip1fl/flLysMCre) characterised by progressive alterations in LSEC phenotype. We implement multiparametric characterisation of LSECs by using novel real-time atomic force microscopy supported with scanning electron microscopy and quantitative fluorescence microscopy. In addition, we provide genetic profiling, searching for characteristic genes encoding proteins that might be connected with the structure of fenestrations. Results We demonstrate that LSECs in Mcpip1fl/flLysMCre display two phases of defenestration: the early phase, with modest defenestration that was fully reversible using cytochalasin B and the late phase, with severe defenestration that is mostly irreversible. By thorough analysis of LSEC porosity, elastic modulus and actin abundance in Mcpip1fl/flLysMCre and in response to cytochalasin B, we demonstrate that proteins other than actin must be additionally responsible for inducing open fenestrations. We highlight several genes that were severely affected in the late but not in the early phase of LSEC defenestration shedding a light on complex structure of individual fenestrations. Conclusions The presented model of LSEC derived from Mcpip1fl/flLysMCre provides a valuable reference for developing novel strategies for LSEC refenestration in the early and late phases of liver pathology.

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Association of dietary intake of theobromine with periodontitis: NHANES 2009-2014

Zhou,

Cai,

et al. 2024

Preprint

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Background: Theobromine intake usually comes from coffee, tea, and cocoa foods. Related studies have shown that theobromine is a bioactive molecule with anti-inflammatory, antithrombotic, anti-fat, and other effects. Periodontitis is a kind of oral inflammatory disease with high incidence, which is characterized by alveolar bone resorption leading to tooth loosening and loss. Therefore, this study aims to investigate whether theobromine intake correlates with periodontitis and whether it is a risk or protective factor for periodontitis. It hopes to provide a basis for theobromine-related diet or drugs to prevent and treat periodontitis. Methods: The study was based on National Health and Nutrition Examination Survey (NHANES) data from 2009–2014. The exposure factor was theobromine, derived from two-day, 24-hour total nutrient intake data from the NHANES dietary data. Periodontitis as an outcome factor was derived from the oral health component of the examination data. We used weighted multiple logistic regression, stratified analysis, and curve fitting to explore the relationship between theobromine dietary intake and periodontitis severity based on weighting and adjusting for confounding factors. Results: After adjusting for relevant confounding factors, weighted logistic regression showed that moderate and high levels of theobromine intake were negatively correlated with periodontitis severity (P < 0.05, OR < 1). Stratified analysis showed that race, BMI, age, diabetes, smoking, family PIR, education, and marital status had an impact on the relationship between theobromine intake and periodontitis. Conclusion: This study demonstrated a negative correlation between theobromine dietary intake and periodontitis, suggesting that theobromine intake may serve as a protective factor against the development of periodontitis.

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Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure

Cited by 4 publications

References 64 publications

Liver sinusoidal endothelial cells rely on oxidative phosphorylation but avoid processing long-chain fatty acids in their mitochondria

Liver sinusoidal endothelial cells rely on oxidative phosphorylation but avoid processing long-chain fatty acids in their mitochondria

Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation

Association of dietary intake of theobromine with periodontitis: NHANES 2009-2014

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