Showing papers in "Cell Metabolism in 2019"

TL;DR: Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.

TL;DR: The metabolic circuitries whereby TAMs condition the TME to support tumor growth and how such pathways can be therapeutically targeted are discussed.

TL;DR: This Review summarizes epigenetic signatures obtained from human tissues of relevance for metabolism—i.e., adipose tissue, skeletal muscle, pancreatic islets, liver, and blood—in relation to obesity and T2D to support not only a role for epigenetics in disease development, but also epigenetic alterations as a response to disease.

TL;DR: The findings that led to these conclusions are reviewed and how this sets the stage for new lines of investigation in which extracellular miRNAs are recognized as important mediators of intercellular communication and potential candidates for therapy of disease.

TL;DR: The evidence for regulators of heat production in thermogenic adipocytes in the context of the thermodynamic and kinetic principles that govern their therapeutic utility is reviewed.

TL;DR: The results suggest that the circadian clock maintains metabolic homeostasis by sustaining daily rhythms in feeding and fasting and by maintaining balance between nutrient and cellular stress responses.

TL;DR: Current knowledge on molecular, cellular, and organismal effects of known and putative CRMs in mice and humans are described and it is anticipated that CRMs will become part of the pharmacological armamentarium against aging and age-related cardiovascular, neurodegenerative, and malignant diseases.

TL;DR: It is reported that cholesterol in the tumor microenvironment induces CD8+ T cell expression of immune checkpoints and exhaustion and a new strategy for restoring T-cell function by reducing cholesterol to enhance T cell-based immunotherapy is suggested.

TL;DR: In this article, the role of NAD+ and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer's, Parkinson's, and Huntington diseases, and amyotrophic lateral sclerosis.

TL;DR: It was found that exposure to amyloid-β triggers acute microglial inflammation accompanied by metabolic reprogramming from oxidative phosphorylation to glycolysis, and it was shown that metabolic boosting with recombinant interferon-γ treatment reversed the defective Glycolytic metabolism and inflammatory functions of microglia, thereby mitigating the AD pathology of 5XFAD mice.

TL;DR: It is found that obesity results in the accumulation of senescent glial cells in proximity to the lateral ventricle, a region in which adult neurogenesis occurs, and that senolytics are a potential new therapeutic avenue for treating neuropsychiatric disorders.

TL;DR: Current concepts about metabolic regulation in tumors are described, focusing on processes intrinsic to cancer cells and on factors imposed upon cancer cells by the tumor microenvironment.

TL;DR: It is demonstrated that macrophages programmed by PDA cells release a spectrum of pyrimidine species, suggesting an unknown physiological role of pyrimidine exchange by immune cells and providing insights into the role of Macrophages in pancreatic cancer therapy.

TL;DR: It is shown that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is associated with up to 60% of individuals with NAFLD in a Chinese cohort, and an alteration in the gut microbiome drives the condition due to excess endogenous alcohol production.

TL;DR: Ablation of STING ameliorated kidney fibrosis in mouse models of chronic kidney disease, demonstrating how TFAM sequesters mtDNA to limit the inflammation leading to fibrosis.

TL;DR: This work aims to emphasize the close relationship between bacterial metabolism and antibiotic efficacy as well as propose areas of exploration to develop novel antibiotics that optimally exploit bacterial metabolic networks.

TL;DR: In vivo isotopic tracing is employed to systemically quantify BCAA oxidation in healthy and insulin-resistant mice, finding that most tissues rapidly oxidize BCAAs into the tricarboxylic acid (TCA) cycle, with the greatest quantity occurring in muscle, brown fat, liver, kidneys, and heart.

TL;DR: A reproducible method is developed to derive multi-cellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells that exhibit transcriptomic resemblance to in vivo-derived tissues that offer a new approach for studying a personalized basis for inflammation and fibrosis in humans.

TL;DR: GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings, and it is demonstrated that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF 15 may induce an aversive response to nutritional stress.

TL;DR: It is reported that SIRT6-deficient cells and tissues accumulate abundant cytoplasmic L1 cDNA, which triggers strong type I interferon response via activation of cGAS, and modulating L1 activity may be an important strategy for attenuating age-related pathologies.

TL;DR: It is proposed that lactate/SLC5A12-induced metabolic reprogramming is a distinctive feature of lymphoid synovitis in rheumatoid arthritis patients and a potential therapeutic target in chronic inflammatory disorders.

TL;DR: It is found that insulin resistance accelerates β cell senescence leading to loss of function and cellular identity and worsening metabolic profile, laying the framework to pursue senolysis of β cells as a preventive and alleviating strategy for T2D.

TL;DR: It is shown that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average, and supports its safety.

TL;DR: There is emerging evidence showing that some drugs are more effective at nighttime than daytime, whereas for others it is the opposite, which suggests that the biology of the target cell will determine how an organ will respond to a drug at a specific time of the day, thus modulating pharmacodynamics.

TL;DR: Initial proof of evidence has been provided that targeting (normalizing) these metabolic perturbations in diseased ECs and delivery of metabolites deserve increasing attention as novel therapeutic approaches for inhibiting or stimulating vessel growth in multiple disorders.

TL;DR: It is found that obesity results in profound perturbation of the metabolome; nearly a third of the assayed metabolites associated with changes in BMI are associated withChanges in BMI.

TL;DR: It is shown that ovarian cancer cells promote membrane-cholesterol efflux and depletion of lipid rafts from macrophages and genetic deletion of ABC transporters reverts the tumor-promoting functions of TAMs and reduces tumor progression.

TL;DR: It is shown persulfidation is an evolutionarily conserved modification and waves of persulfide are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function, and an age-associated decline is reported that is conserved across evolutionary boundaries.

TL;DR: It is shown that the circulating levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) significantly decline with age in mice and humans, and a novel EV-mediated delivery mechanism is revealed which promotes systemic NAD+ biosynthesis and counteracts aging, suggesting a potential avenue for anti-aging intervention in humans.

TL;DR: It is shown that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP), and clearance of senescent beta cells could be a new therapeutic approach for T1d.