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Biochimica Et Biophysica Acta.... Nov 2020Carotenoids exert a rich variety of physiological functions in mammals and are beneficial for human health. These lipids are acquired from the diet and metabolized to... (Review)
Review
Carotenoids exert a rich variety of physiological functions in mammals and are beneficial for human health. These lipids are acquired from the diet and metabolized to apocarotenoids, including retinoids (vitamin A and its metabolites). The small intestine is a major site for their absorption and bioconversion. From here, carotenoids and their metabolites are distributed within the body in triacylglycerol-rich lipoproteins to support retinoid signaling in peripheral tissues and photoreceptor function in the eyes. In recent years, much progress has been made in identifying carotenoid metabolizing enzymes, transporters, and binding proteins. A diet-responsive regulatory network controls the activity of these components and adapts carotenoid absorption and bioconversion to the bodily requirements of these lipids. Genetic variability in the genes encoding these components alters carotenoid homeostasis and is associated with pathologies. We here summarize the advanced state of knowledge about intestinal carotenoid metabolism and its impact on carotenoid and retinoid homeostasis of other organ systems, including the eyes, liver, and immune system. The implication of the findings for science-based intake recommendations for these essential dietary lipids is discussed. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.
Topics: Animals; Carotenoids; Homeostasis; Humans; Intestinal Absorption; Lipid Metabolism; Lipids; Liver; Triglycerides; Vitamin A
PubMed: 31794861
DOI: 10.1016/j.bbalip.2019.158580 -
Genes Jul 2021Plants are sessile organisms that need to adapt to constantly changing environmental conditions. Unpredictable climate change places plants under a variety of abiotic... (Review)
Review
Plants are sessile organisms that need to adapt to constantly changing environmental conditions. Unpredictable climate change places plants under a variety of abiotic stresses. Studying the regulation of stress-responsive genes can help to understand plants' ability to adapt to fluctuating environmental conditions. Changes in epigenetic marks such as histone modifications and DNA methylation are known to regulate gene expression by their dynamic variation in response to stimuli. This can then affect their phenotypic plasticity, which helps with the adaptation of plants to adverse conditions. Epigenetic marks may also provide a mechanistic basis for stress memory, which enables plants to respond more effectively and efficiently to recurring stress and prepare offspring for potential future stresses. Studying epigenetic changes in addition to genetic factors is important to better understand the molecular mechanisms underlying plant stress responses. This review summarizes the epigenetic mechanisms behind plant responses to some main abiotic stresses.
Topics: DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Plant; Histones; Plants; Stress, Physiological
PubMed: 34440280
DOI: 10.3390/genes12081106 -
Journal of Thrombosis and Haemostasis :... Jan 2023Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the...
BACKGROUND
Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the effects of TMAO on the metabolism of and response to clopidogrel.
OBJECTIVES
To determine whether choline and TMAO could significantly impair metabolic activation of and platelet response to clopidogrel in choline- or TMAO-fed mice and the mechanisms involved.
METHODS
Male mice were fed with vehicle control (Ctrl), TMAO, choline alone or in combination with 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 for 14 days and then treated with Ctrl or a single oral dose of clopidogrel. Plasma TMAO, protein levels of clopidogrel-metabolizing enzymes in the liver, plasma concentrations of clopidogrel and its metabolites, and adenosine diphosphate-induced platelet aggregation and activation were measured. In addition, HepG2 cells were treated with Ctrl or TMAO alone or in combination with N-acetyl-L-cysteine, ML385, or apocynin, and CES1, reactive oxygen species (ROS), and Nrf2 protein levels were measured, respectively.
RESULTS
TMAO significantly increased Ces1 protein expression and activity and clopidogrel hydrolysis in the liver as well as intracellular ROS and CES1 levels and Nrf2 nucleus translocation in HepG2 cells but decreased the formation of clopidogrel active metabolite and impaired platelet response to clopidogrel. Furthermore, concomitant use of 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 effectively reversed choline- or TMAO-induced impairment of inhibition of platelet aggregation by clopidogrel in mice, respectively.
CONCLUSIONS
Choline and TMAO impair the metabolic activation of and platelet response to clopidogrel through the activation of the NOX-dependent ROS/Nrf2/CES1 pathway, suggesting novel strategies for overcoming clopidogrel resistance from bench to bedside.
Topics: Male; Animals; Mice; Choline; Clopidogrel; NF-E2-Related Factor 2; Reactive Oxygen Species; Activation, Metabolic; Acetylcysteine
PubMed: 36695375
DOI: 10.1016/j.jtha.2022.10.010 -
Frontiers in Immunology 2023Dendritic cells (DCs) are antigen-presenting cells that bridge innate and adaptive immune responses. Multiple cell types, including DCs, rely on cellular metabolism to... (Review)
Review
Dendritic cells (DCs) are antigen-presenting cells that bridge innate and adaptive immune responses. Multiple cell types, including DCs, rely on cellular metabolism to determine their fate. DCs substantially alter cellular metabolic pathways during activation, such as oxidative phosphorylation, glycolysis, fatty acid and amino acid metabolism, which have crucial implications for their functionality. In this review, we summarize and discuss recent progress in DC metabolic studies, focusing on how metabolic reprogramming influences DC activation and functionality and the potential metabolic differences among DC subsets. Improving the understanding of the relationship between DC biology and metabolic regulation may provide promising therapeutic targets for immune-mediated inflammatory diseases.
Topics: Humans; Dendritic Cells; Glycolysis; Oxidative Phosphorylation; Immunity; Inflammation
PubMed: 36969180
DOI: 10.3389/fimmu.2023.1140749 -
The Journal of Nutrition Nov 2021Metabolic abnormalities substantially increase the risk of noncommunicable diseases, which are among the leading causes of mortality globally. Mitigating and preventing...
Metabolic abnormalities substantially increase the risk of noncommunicable diseases, which are among the leading causes of mortality globally. Mitigating and preventing these adverse consequences remains challenging due to a limited understanding of metabolic health. Metabolic flexibility, a key tenet of metabolic health, encompasses the responsiveness of interrelated pathways to maintain energy homeostasis throughout daily physiologic challenges, such as the response to meal challenges. One critical underlying research gap concerns the measurement of postprandial metabolic flexibility, which remains incompletely understood. We concisely review the methodology for assessment of postprandial metabolic flexibility in recent human studies. We identify 3 commonalities of study design, specifically the nature of the challenge, nature of the response measured, and approach to data analysis. Primary interventions were acute short-term nutrition challenges, including single- and multiple-macronutrient tolerance tests. Postmeal challenge responses were measured via laboratory assays and instrumentation, based on a diverse set of metabolic flexibility indicators [e.g., energy expenditure (whole-body indirect calorimetry), glucose and insulin kinetics, metabolomics, transcriptomics]. Common standard approaches have been diabetes-centric with single-macronutrient challenges (oral-glucose-tolerance test) to characterize the postprandial response based on glucose and insulin metabolism; or broad measurements of energy expenditure with calculated macronutrient oxidation via indirect calorimetry. Recent methodological advances have included the use of multiple-macronutrient meal challenges that are more representative of physiologic meals consumed by free-living humans, combinatorial approaches for assays and instruments, evaluation of other metabolic flexibility indicators via precision health, systems biology, and temporal perspectives. Omics studies have identified potential novel indicators of metabolic flexibility, which provide greater granularity to prior evidence from canonical approaches. In summary, recent findings indicate the potential for an expanded understanding of postprandial metabolic flexibility, based on nonclassical measurements and methodology, which could represent novel dynamic indicators of metabolic diseases.
Topics: Blood Glucose; Calorimetry, Indirect; Cross-Over Studies; Energy Metabolism; Humans; Insulin; Meals; Postprandial Period
PubMed: 34293154
DOI: 10.1093/jn/nxab263 -
Trends in Cell Biology Aug 2021Peroxisomes are involved in multiple metabolic processes, including fatty acid oxidation, ether lipid synthesis, and reactive oxygen species (ROS) metabolism. Recent... (Review)
Review
Peroxisomes are involved in multiple metabolic processes, including fatty acid oxidation, ether lipid synthesis, and reactive oxygen species (ROS) metabolism. Recent studies suggest that peroxisomes are critical mediators of cellular responses to various forms of stress, including oxidative stress, hypoxia, starvation, cold exposure, and noise. As dynamic organelles, peroxisomes can modulate their proliferation, morphology, and movement within cells, and engage in crosstalk with other organelles in response to external cues. Although peroxisome-derived hydrogen peroxide has a key role in cellular signaling related to stress, emerging studies suggest that other products of peroxisomal metabolism, such as acetyl-CoA and ether lipids, are also important for metabolic adaptation to stress. Here, we review molecular mechanisms through which peroxisomes regulate metabolic and environmental stress.
Topics: Lipid Metabolism; Oxidation-Reduction; Oxidative Stress; Peroxisomes; Reactive Oxygen Species
PubMed: 33674166
DOI: 10.1016/j.tcb.2021.02.005