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Antioxidants & Redox Signaling May 2022Altered plasma triglyceride metabolism and changes in dietary fatty acid types and levels are major contributors to the development of metabolic and cardiovascular... (Review)
Review
Altered plasma triglyceride metabolism and changes in dietary fatty acid types and levels are major contributors to the development of metabolic and cardiovascular diseases such as fatty liver disease, obesity, diabetes, and atherosclerosis. Lipid accumulation in visceral adipose tissue and ectopically in other organs, as well as lipid-induced redox imbalance, is connected to mitochondrial dysfunction in a range of oxidative stress-associated metabolic and degenerative disorders. Successful mitochondrial adaptive responses in the context of hypertriglyceridemia and dietary bioactive polyunsaturated fatty acids contribute to increase body energy expenditure and reduce oxidative stress, thus allowing several cell types to cope with metabolic challenges and stresses. These responses include mitochondrial redox signaling, mild uncoupling, and changes in network dynamic behavior. Mitochondrial bioenergetics and redox changes in a lipid overload context are relatively well characterized. However, the turning point between adaptive and maladaptive mitochondrial responses remains a critical issue to be elucidated. In addition, the relationship between changes in fusion/fission machinery and mitochondrial function is less well understood. The effective mitochondrial responses described here support the research for new drug design and diet or nutraceutical formulations targeting mitochondrial mild uncoupling and effective quality control as putative strategies for cardiometabolic diseases. 36, 953-968.
Topics: Cell Respiration; Energy Metabolism; Humans; Hypertriglyceridemia; Lipids; Mitochondria
PubMed: 34409856
DOI: 10.1089/ars.2021.0180 -
Phytochemistry Sep 2022Microalgae are important primary producers and form the basis for the marine food web. As global climate changes, so do salinity levels that algae are exposed to. A...
Microalgae are important primary producers and form the basis for the marine food web. As global climate changes, so do salinity levels that algae are exposed to. A metabolic response of algal cells partly alleviates the resulting osmotic stress. Some metabolites involved in the response are well studied, but the full metabolic implications of adaptation remain unclear. Improved analytical methodology provides an opportunity for additional insight. We can now follow responses to stress in major parts of the metabolome and derive comprehensive charts of the resulting metabolic re-wiring. In this study, we subjected three species of diatoms to high salinity conditions and compared their metabolome to controls in an untargeted manner. The three well-investigated species with sequenced genomes Phaeodactylum tricornutum, Thalassiosira pseudonana, and Skeletonema marinoi were selected for our survey. The microalgae react to salinity stress with common adaptations in the metabolome by amino acid up-regulation, production of saccharides, and inositols. But also species-specific dysregulation of metabolites is common. Several metabolites previously not connected with osmotic stress reactions are identified, including 4-hydroxyproline, pipecolinic acid, myo-inositol, threonic acid, and acylcarnitines. This expands our knowledge about osmoadaptation and calls for further functional characterization of metabolites and pathways in algal stress physiology.
Topics: Acclimatization; Diatoms; Metabolome; Microalgae; Salinity
PubMed: 35671808
DOI: 10.1016/j.phytochem.2022.113267 -
Molecular Metabolism Mar 2020It has been known for close to a century that, on average, tumors have a metabolism that is different from those found in healthy tissues. Typically, tumors show a... (Review)
Review
BACKGROUND
It has been known for close to a century that, on average, tumors have a metabolism that is different from those found in healthy tissues. Typically, tumors show a biosynthetic metabolism that distinguishes itself by engaging in large scale aerobic glycolysis, heightened flux through the pentose phosphate pathway, and increased glutaminolysis among other means. However, it is becoming equally clear that non tumorous tissues at times can engage in similar metabolism, while tumors show a high degree of metabolic flexibility reacting to cues, and stresses in their local environment.
SCOPE OF THE REVIEW
In this review, we want to scrutinize historic and recent research on metabolism, comparing and contrasting oncogenic and physiological metabolic states. This will allow us to better define states of bona fide tumor metabolism. We will further contextualize the stress response and the metabolic evolutionary trajectory seen in tumors, and how these contribute to tumor progression. Lastly, we will analyze the implications of these characteristics with respect to therapy response.
MAJOR CONCLUSIONS
In our review, we argue that there is not one single oncogenic state, but rather a diverse set of oncogenic states. These are grounded on a physiological proliferative/wound healing program but distinguish themselves due to their large scale of proliferation, mutations, and transcriptional changes in key metabolic pathways, and the adaptations to widespread stress signals within tumors. We find evidence for the necessity of metabolic flexibility and stress responses in tumor progression and how these responses in turn shape oncogenic progression. Lastly, we find evidence for the notion that the metabolic adaptability of tumors frequently frustrates therapeutic interventions.
Topics: Cell Proliferation; Citric Acid Cycle; Energy Metabolism; Glucose; Glycolysis; Humans; Metabolic Networks and Pathways; Mutation; Neoplasm Invasiveness; Neoplasms; Pentose Phosphate Pathway; Tumor Escape
PubMed: 31668988
DOI: 10.1016/j.molmet.2019.08.021 -
Experimental & Molecular Medicine Sep 2023Adipose tissue is a dynamic and metabolically active organ that plays a crucial role in energy homeostasis and endocrine function. Recent advancements in lipidomics... (Review)
Review
Adipose tissue is a dynamic and metabolically active organ that plays a crucial role in energy homeostasis and endocrine function. Recent advancements in lipidomics techniques have enabled the study of the complex lipid composition of adipose tissue and its role in metabolic disorders such as obesity, diabetes, and cardiovascular disease. In addition, adipose tissue lipidomics has emerged as a powerful tool for understanding the molecular mechanisms underlying these disorders and identifying bioactive lipid mediators and potential therapeutic targets. This review aims to summarize recent lipidomics studies that investigated the dynamic remodeling of adipose tissue lipids in response to specific physiological changes, pharmacological interventions, and pathological conditions. We discuss the molecular mechanisms of lipid remodeling in adipose tissue and explore the recent identification of bioactive lipid mediators generated in adipose tissue that regulate adipocytes and systemic metabolism. We propose that manipulating lipid-mediator metabolism could serve as a therapeutic approach for preventing or treating obesity-related metabolic diseases.
Topics: Humans; Adipose Tissue; Adipocytes; Obesity; Diabetes Mellitus; Metabolic Diseases; Lipid Metabolism; Lipids
PubMed: 37653032
DOI: 10.1038/s12276-023-01071-4 -
Annual Review of Immunology Apr 2020Metabolism is one of the strongest drivers of interkingdom interactions-including those between microorganisms and their multicellular hosts. Traditionally thought to... (Review)
Review
Metabolism is one of the strongest drivers of interkingdom interactions-including those between microorganisms and their multicellular hosts. Traditionally thought to fuel energy requirements and provide building blocks for biosynthetic pathways, metabolism is now appreciated for its role in providing metabolites, small-molecule intermediates generated from metabolic processes, to perform various regulatory functions to mediate symbiotic relationships between microbes and their hosts. Here, we review recent advances in our mechanistic understanding of how microbiota-derived metabolites orchestrate and support physiological responses in the host, including immunity, inflammation, defense against infections, and metabolism. Understanding how microbes metabolically communicate with their hosts will provide us an opportunity to better describe how a host interacts with all microbes-beneficial, pathogenic, and commensal-and an opportunity to discover new ways to treat microbial-driven diseases.
Topics: Animals; Disease Susceptibility; Energy Metabolism; Homeostasis; Host-Pathogen Interactions; Humans; Immune System; Microbiota; Symbiosis
PubMed: 32340573
DOI: 10.1146/annurev-immunol-071219-125715 -
Immunological Reviews May 2024Over the past decade, there has been a surge in discoveries of how metabolic pathways regulate immune cell function in health and disease, establishing the field of... (Review)
Review
Over the past decade, there has been a surge in discoveries of how metabolic pathways regulate immune cell function in health and disease, establishing the field of immunometabolism. Specifically, pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, and those involving lipid metabolism have been implicated in regulating immune cell function. Viral infections cause immunometabolic changes which lead to antiviral immunity, but little is known about how metabolic changes regulate interferon responses. Interferons are critical cytokines in host defense, rapidly induced upon pathogen recognition, but are also involved in autoimmune diseases. This review summarizes how metabolic change impacts interferon production. We describe how glycolysis, lipid metabolism (specifically involving eicosanoids and cholesterol), and the TCA cycle-linked intermediates itaconate and fumarate impact type I interferons. Targeting these metabolic changes presents new therapeutic possibilities to modulate type I interferons during host defense or autoimmune disorders.
Topics: Humans; Interferon Type I; Animals; Lipid Metabolism; Glycolysis; Citric Acid Cycle; Virus Diseases; Autoimmune Diseases; Signal Transduction; Energy Metabolism
PubMed: 38465724
DOI: 10.1111/imr.13318 -
Molecular Metabolism Aug 2020ATP-dependent chromatin remodelers are evolutionarily conserved complexes that alter nucleosome positioning to influence many DNA-templated processes, such as... (Review)
Review
BACKGROUND
ATP-dependent chromatin remodelers are evolutionarily conserved complexes that alter nucleosome positioning to influence many DNA-templated processes, such as replication, repair, and transcription. In particular, chromatin remodeling can dynamically regulate gene expression by altering accessibility of chromatin to transcription factors.
SCOPE OF REVIEW
This review provides an overview of the importance of chromatin remodelers in the regulation of metabolic gene expression. Particular emphasis is placed on the INO80 and SWI/SNF (BAF/PBAF) chromatin remodelers in both yeast and mammals. This review details discoveries from the initial identification of chromatin remodelers in Saccharomyces cerevisiae to recent discoveries in the metabolic requirements of developing embryonic tissues in mammals.
MAJOR CONCLUSIONS
INO80 and SWI/SNF (BAF/PBAF) chromatin remodelers regulate the expression of energy metabolism pathways in S. cerevisiae and mammals in response to diverse nutrient environments. In particular, the INO80 complex organizes the temporal expression of gene expression in the metabolically synchronized S. cerevisiae system. INO80-mediated chromatin remodeling is also needed to constrain cell division during metabolically favorable conditions. Conversely, the BAF/PBAF remodeler regulates tissue-specific glycolytic metabolism and is disrupted in cancers that are dependent on glycolysis for proliferation. The role of chromatin remodeling in metabolic gene expression is downstream of the metabolic signaling pathways, such as the TOR pathway, a critical regulator of metabolic homeostasis. Furthermore, the INO80 and BAF/PBAF chromatin remodelers have both been shown to regulate heart development, the tissues of which have unique requirements for energy metabolism during development. Collectively, these results demonstrate that chromatin remodelers communicate metabolic status to chromatin and are a central component of homeostasis pathways that optimize cell fitness, organismal development, and prevent disease.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; DNA-Binding Proteins; Gene Expression; Gene Expression Regulation; Metabolic Networks and Pathways; Metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Transcription Factors; Transcriptional Activation
PubMed: 32251664
DOI: 10.1016/j.molmet.2020.100973 -
Journal of Applied Physiology... Aug 2023We assessed the feasibility of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) human adult clinical exercise protocols, while also documenting select...
We assessed the feasibility of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) human adult clinical exercise protocols, while also documenting select cardiovascular, metabolic, and molecular responses to these protocols. After phenotyping and familiarization sessions, 20 subjects (25 ± 2 yr, 12 M, 8 W) completed an endurance exercise bout ( = 8, 40 min cycling at 70% V̇o), a resistance exercise bout ( = 6, ∼45 min, 3 sets of ∼10 repetition maximum, 8 exercises), or a resting control period ( = 6, 40 min rest). Blood samples were taken before, during, and after (10 min, 2 h, and 3.5 h) exercise or rest for levels of catecholamines, cortisol, glucagon, insulin, glucose, free fatty acids, and lactate. Heart rate was recorded throughout exercise (or rest). Skeletal muscle (vastus lateralis) and adipose (periumbilical) biopsies were taken before and ∼4 h following exercise or rest for mRNA levels of genes related to energy metabolism, growth, angiogenesis, and circadian processes. Coordination of the timing of procedural components (e.g., local anesthetic delivery, biopsy incisions, tumescent delivery, intravenous line flushes, sample collection and processing, exercise transitions, and team dynamics) was reasonable to orchestrate while considering subject burden and scientific objectives. The cardiovascular and metabolic alterations reflected a dynamic and unique response to endurance and resistance exercise, whereas skeletal muscle was transcriptionally more responsive than adipose 4 h postexercise. In summary, the current report provides the first evidence of protocol execution and feasibility of key components of the MoTrPAC human adult clinical exercise protocols. Scientists should consider designing exercise studies in various populations to interface with the MoTrPAC protocols and DataHub. This study highlights the feasibility of key aspects of the MoTrPAC adult human clinical protocols. This initial preview of what can be expected from acute exercise trial data from MoTrPAC provides an impetus for scientists to design exercise studies to interlace with the rich phenotypic and -omics data that will populate the MoTrPAC DataHub at the completion of the parent protocol.
Topics: Adult; Humans; Feasibility Studies; Exercise; Muscle, Skeletal; Quadriceps Muscle; Energy Metabolism
PubMed: 37318985
DOI: 10.1152/japplphysiol.00210.2023