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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 -
Molecules (Basel, Switzerland) Jul 2016In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and... (Review)
Review
In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state remain fragmentary, it is well documented that in natural settings microorganisms are mainly found in association with surfaces, which results in biofilm formation. Biofilms are characterized by genetic and physiological heterogeneity and the occurrence of altered microenvironments within the matrix. Microbial cells in communities display a variety of metabolic differences as compared to their free-living counterparts. Immobilization of bacteria can occur either as a natural phenomenon or as an artificial process. The majority of changes observed in immobilized cells result from protection provided by the supports. Knowledge about the main physiological responses occurring in immobilized cells may contribute to improving the efficiency of immobilization techniques. This paper reviews the main metabolic changes exhibited by immobilized bacterial cells, including growth rate, biodegradation capabilities, biocatalytic efficiency and plasmid stability.
Topics: Bacteria; Bacteriological Techniques; Biocatalysis; Biodegradation, Environmental; Biofilms; Biotransformation; Cell Culture Techniques; Cells, Immobilized; Energy Metabolism; Gene Expression Regulation, Bacterial; Genomic Instability; Plasmids
PubMed: 27455220
DOI: 10.3390/molecules21070958 -
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 -
International Journal of Molecular... Feb 2021The metabolic microenvironment, comprising all soluble and insoluble nutrients and co-factors in the extracellular milieu, has a major impact on cancer cell... (Review)
Review
The metabolic microenvironment, comprising all soluble and insoluble nutrients and co-factors in the extracellular milieu, has a major impact on cancer cell proliferation and survival. A large body of evidence from recent studies suggests that tumor cells show a high degree of metabolic flexibility and adapt to variations in nutrient availability. Insufficient vascular networks and an imbalance of supply and demand shape the metabolic tumor microenvironment, which typically contains a lower concentration of glucose compared to normal tissues. The present review sheds light on the recent literature on adaptive responses in cancer cells to nutrient deprivation. It focuses on the utilization of alternative nutrients in anabolic metabolic pathways in cancer cells, including soluble metabolites and macromolecules and outlines the role of central metabolic enzymes conferring metabolic flexibility, like gluconeogenesis enzymes. Moreover, a conceptual framework for potential therapies targeting metabolically flexible cancer cells is presented.
Topics: Gluconeogenesis; Humans; Metabolic Networks and Pathways; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 33540663
DOI: 10.3390/ijms22031476 -
Trends in Biochemical Sciences Nov 2023Biomembranes are complex materials composed of lipids and proteins that compartmentalize biochemistry. They are actively remodeled in response to physical and metabolic... (Review)
Review
Biomembranes are complex materials composed of lipids and proteins that compartmentalize biochemistry. They are actively remodeled in response to physical and metabolic cues, as well as during cell differentiation and stress. The concept of homeoviscous adaptation has become a textbook example of membrane responsiveness. Here, we discuss limitations and common misconceptions revolving around it. By highlighting key moments in the life cycle of a transmembrane protein, we illustrate that membrane thickness and a finely regulated membrane compressibility are crucial to facilitate proper membrane protein insertion, function, sorting, and inheritance. We propose that the unfolded protein response (UPR) provides a mechanism for endoplasmic reticulum (ER) membrane homeostasis by sensing aberrant transverse membrane stiffening and triggering adaptive responses that re-establish membrane compressibility.
Topics: Endoplasmic Reticulum Stress; Unfolded Protein Response; Homeostasis; Endoplasmic Reticulum; Membrane Proteins
PubMed: 37652754
DOI: 10.1016/j.tibs.2023.08.004 -
Cells Dec 2019The myeloid lineage consists of multiple immune cell types, such as macrophages, monocytes, and dendritic cells. It actively participates in both innate and adaptive... (Review)
Review
The myeloid lineage consists of multiple immune cell types, such as macrophages, monocytes, and dendritic cells. It actively participates in both innate and adaptive immunity. In response to pro- or anti-inflammatory signals, these cells undergo distinct programmed metabolic changes especially in mitochondria. Pro-inflammatory signals induce not only a simple shift from oxidative phosphorylation to glycolysis, but also complicated metabolic alterations during the early and tolerant stages in myeloid cells. In mitochondria, a broken Krebs cycle leads to the accumulation of two metabolites, citrate and succinate, both of which trigger pro-inflammatory responses of myeloid cells. A deficient electron transport chain induces pro-inflammatory responses in the resting myeloid cells while it suppresses these responses in the polarized cells during inflammation. The metabolic reprogramming in mitochondria is also associated with altered mitochondrial morphology. On the other hand, intact oxidative phosphorylation is required for the anti-inflammatory functions of myeloid cells. Fatty acid synthesis is essential for the pro-inflammatory effect and glutamine metabolism in mitochondria exhibits the anti-inflammatory effect. A few aspects of metabolic reprogramming remain uncertain, for example, glycolysis and fatty acid oxidation in anti-inflammation. Overall, metabolic reprogramming is an important element of immune responses in myeloid cells.
Topics: Adaptive Immunity; Citric Acid Cycle; Glycolysis; Humans; Immunity, Innate; Mitochondria; Myeloid Cells; Oxidative Phosphorylation
PubMed: 31861356
DOI: 10.3390/cells9010005 -
MBio Mar 2019Macrophages are the primary targets of infection; the early events of macrophage interaction with define subsequent progression and outcome of infection. can alter... (Review)
Review
Macrophages are the primary targets of infection; the early events of macrophage interaction with define subsequent progression and outcome of infection. can alter the innate immunity of macrophages, resulting in suboptimal Th1 immunity, which contributes to the survival, persistence, and eventual dissemination of the pathogen. Recent advances in immunometabolism illuminate the intimate link between the metabolic states of immune cells and their specific functions. In this review, we describe the little-studied biphasic metabolic dynamics of the macrophage response during progression of infection by and discuss their relevance to macrophage immunity and pathogenicity. The early phase of macrophage infection, which is marked by M1 polarization, is accompanied by a metabolic switch from mitochondrial oxidative phosphorylation to hypoxia-inducible factor 1 alpha (HIF-1α)-mediated aerobic glycolysis (also known as the Warburg effect in cancer cells), as well as by an upregulation of pathways involving oxidative and antioxidative defense responses, arginine metabolism, and synthesis of bioactive lipids. These early metabolic changes are followed by a late adaptation/resolution phase in which macrophages transition from glycolysis to mitochondrial oxidative metabolism, with a consequent dampening of macrophage proinflammatory and antimicrobial responses. Importantly, the identification of upregulated metabolic pathways and/or metabolic regulatory mechanisms with immunomodulatory functions during M1 polarization has revealed novel mechanisms of pathogenicity. These advances can lead to the development of novel host-directed therapies to facilitate bacterial clearance in tuberculosis by targeting the metabolic state of immune cells.
Topics: Aerobiosis; Animals; Glycolysis; Host-Pathogen Interactions; Humans; Macrophages; Mycobacterium tuberculosis; Oxidative Phosphorylation; Tuberculosis
PubMed: 30914513
DOI: 10.1128/mBio.02550-18 -
ASN Neuro Jul 2012Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for... (Review)
Review
Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron-astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models.
Topics: Animals; Brain; Energy Metabolism; Glucose; Humans
PubMed: 22612861
DOI: 10.1042/AN20120021 -
International Journal of Environmental... Aug 2022The relationship between volume training of resistance training (RT), body composition and cardiometabolic profile in menopausal women is poorly understand. This study...
The relationship between volume training of resistance training (RT), body composition and cardiometabolic profile in menopausal women is poorly understand. This study aimed to evaluate the dose−response relationship of RT on lipid profile, body composition and metabolic phenotypes in menopausal women. A total of 31 women were categorized according to different volume of RT. Body composition was evaluated by DEXA and the cardiometabolic risk by metabolic phenotypes and lipid profile. There was a higher frequency of metabolically unhealthy phenotype in women who practiced RT for less than two years and had a weekly frequency lower than three days a week (p > 0.05). Women with more than two years and a higher weekly frequency of RT had lower trunk fat mass than their counterparties (15.33 ± 7.56 versus 10.57 ± 4.87, p = 0.04; 16.31 ± 7.46 versus 10.98 ± 5.49, p = 0.03, respectively). There was an association between HDL-c and time of RT in years. A moderate correlation was identified between variables of body adiposity, time in years and weekly frequency of RT. The present study concludes that more time in years and weekly frequency of RT practice are associated with lower body adiposity in menopausal women, the first also being associated with HDL-c.
Topics: Body Composition; Body Mass Index; Cardiovascular Diseases; Female; Humans; Lipids; Menopause; Obesity; Phenotype; Resistance Training
PubMed: 36012004
DOI: 10.3390/ijerph191610369