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Frontiers in Endocrinology 2023The ability to generate thermogenic fat could be a targeted therapy to thwart obesity and improve metabolic health. Brown and beige adipocytes are two types of... (Review)
Review
The ability to generate thermogenic fat could be a targeted therapy to thwart obesity and improve metabolic health. Brown and beige adipocytes are two types of thermogenic fat cells that regulate energy balance. Both adipocytes share common morphological, biochemical, and thermogenic properties. Yet, recent evidence suggests unique features exist between brown and beige adipocytes, such as their cellular origin and thermogenic regulatory processes. Beige adipocytes also appear highly plastic, responding to environmental stimuli and interconverting between beige and white adipocyte states. Additionally, beige adipocytes appear to be metabolically heterogenic and have substrate specificity. Nevertheless, obese and aged individuals cannot develop beige adipocytes in response to thermogenic fat-inducers, creating a key clinical hurdle to their therapeutic promise. Thus, elucidating the underlying developmental, molecular, and functional mechanisms that govern thermogenic fat cells will improve our understanding of systemic energy regulation and strive for new targeted therapies to generate thermogenic fat. This review will examine the recent advances in thermogenic fat biogenesis, molecular regulation, and the potential mechanisms for their failure.
Topics: Humans; Aged; Adipocytes; Adipose Tissue, Brown; Adipocytes, Beige; Energy Metabolism; Obesity
PubMed: 37020585
DOI: 10.3389/fendo.2023.1150059 -
International Journal of Molecular... May 2022Cancer is the second most common cause of death worldwide after cardiovascular diseases. The development of molecular and biochemical techniques has expanded the... (Review)
Review
Cancer is the second most common cause of death worldwide after cardiovascular diseases. The development of molecular and biochemical techniques has expanded the knowledge of changes occurring in specific metabolic pathways of cancer cells. Increased aerobic glycolysis, the promotion of anaplerotic responses, and especially the dependence of cells on glutamine and fatty acid metabolism have become subjects of study. Despite many cancer treatment strategies, many patients with neoplastic diseases cannot be completely cured due to the development of resistance in cancer cells to currently used therapeutic approaches. It is now becoming a priority to develop new treatment strategies that are highly effective and have few side effects. In this review, we present the current knowledge of the enzymes involved in the different steps of glycolysis, the Krebs cycle, and the pentose phosphate pathway, and possible targeted therapies. The review also focuses on presenting the differences between cancer cells and normal cells in terms of metabolic phenotype. Knowledge of cancer cell metabolism is constantly evolving, and further research is needed to develop new strategies for anti-cancer therapies.
Topics: Citric Acid Cycle; Energy Metabolism; Glycolysis; Humans; Neoplasms; Pentose Phosphate Pathway
PubMed: 35628385
DOI: 10.3390/ijms23105572 -
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 -
Cellular & Molecular Biology Letters 2020Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and... (Review)
Review
Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid β-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.
Topics: Energy Metabolism; Fatty Acid Synthases; Glucose; Glycolysis; Host-Pathogen Interactions; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Influenza, Human; Interferons; Lipid Metabolism; Metabolic Networks and Pathways; Nitric Oxide
PubMed: 32161622
DOI: 10.1186/s11658-020-00211-2 -
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 -
American Journal of Physiology. Cell... Apr 2022Redox homeostasis is elemental for the normal physiology of all cell types. Cells use multiple mechanisms to tightly regulate the redox balance. The onset and... (Review)
Review
Redox homeostasis is elemental for the normal physiology of all cell types. Cells use multiple mechanisms to tightly regulate the redox balance. The onset and progression of many metabolic and aging-associated diseases occur due to the dysregulation of redox homeostasis. Thus, it is critical to identify and therapeutically target mechanisms that precipitate abnormalities in redox balance. Reactive oxygen species (ROS) produced within the immune cells regulate homeostasis, hyperimmune and hypoimmune cell responsiveness, apoptosis, immune response to pathogens, and tumor immunity. Immune cells have both cytosolic and organelle-specific redox regulatory systems to maintain appropriate levels of ROS. Nicotinamide nucleotide transhydrogenase (NNT) is an essential mitochondrial redox regulatory protein. Dysregulation of NNT function prevents immune cells from mounting an adequate immune response to pathogens, promotes a chronic inflammatory state associated with aging and metabolic diseases, and initiates conditions related to a dysregulated immune system such as autoimmunity. Although many studies have reported on NNT in different cell types, including cancer cells, relatively few studies have explored NNT in immune cells. This review provides an overview of NNT and focuses on the current knowledge of NNT in the immune cells.
Topics: Mitochondria; Mitochondrial Proteins; NADP Transhydrogenases; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 35138175
DOI: 10.1152/ajpcell.00607.2020 -
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 -
Cells Nov 2023Cancer stem cells (CSCs) are a rare cancer cell population, responsible for the facilitation, progression, and resistance of tumors to therapeutic interventions. This... (Review)
Review
Cancer stem cells (CSCs) are a rare cancer cell population, responsible for the facilitation, progression, and resistance of tumors to therapeutic interventions. This subset of cancer cells with stemness and tumorigenic properties is organized in niches within the tumor microenvironment (TME) and presents altered regulation in a variety of metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS), as well as lipid, amino acid, and iron metabolism. CSCs exhibit similarities as well as differences when comparedto normal stem cells, but also possess the ability of metabolic plasticity. In this review, we summarize the metabolic characteristics of normal, non-cancerous stem cells and CSCs. We also highlight the significance and implications of interventions targeting CSC metabolism to potentially achieve more robust clinical responses in the future.
Topics: Humans; Neoplasms; Neoplastic Stem Cells; Glycolysis; Metabolic Networks and Pathways; Metabolome; Tumor Microenvironment
PubMed: 38067114
DOI: 10.3390/cells12232686