Getting Warmer: Following One's Gut to Build Bone.
Abstract In this issue of the Cell Metabolism, Chevalier et al. show that a warm environment produces changes in the composition of intestinal microbiota and that these changes can prevent bone loss due to hypogonadism. Dovetailing with prior studies on the ability of probiotics to reverse hypogonadism-induced osteopenia, the findings reaffirm a central role for the microbiome in regulating bone mass in response to both environmental and hormonal cues. PMID: 33027670 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Iqbal J, Yuen T, Zaidi M Tags: Cell Metab Source Type: research

Where Mitochondria Meet Autoimmunity: The Treg Cell Link.
Abstract Although a crucial role for mitochondrial metabolism in controlling T regulatory (Treg) cell function has been recognized, its contribution during autoimmunity has not yet been fully elucidated. In this issue of Cell Metabolism, Alissafi and colleagues demonstrate that during autoimmunity, Treg cell functional alterations associate with mitochondrial oxidative stress, dysfunctional mitophagy, and enhanced DNA damage response, culminating with their cell death. PMID: 33027671 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Procaccini C, Matarese G Tags: Cell Metab Source Type: research

Language of a Long-Term Relationship: Bacterial Inositols and the Intestinal Epithelium.
Abstract The exact principles guiding host-microbe homeostasis in the intestinal tract remain obscure. In a recent issue of Nature, Wu et al. (2020) describe that bacterial-derived inositols are an important principle that shapes regenerative properties of the colonic epithelium. The metabolites activate HDAC3, which represents an important part of the epigenetic machinery. PMID: 33027672 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Fazio A, Rosenstiel P Tags: Cell Metab Source Type: research

Mitochondrial Ejection for Cardiac Protection: The Macrophage Connection.
Abstract Mitochondrial dysfunction is a hallmark of heart disease. Nicolás-Ávila et al. (2020) now find that cardiomyocytes eject dysfunctional mitochondria in exopher vesicles, which require elimination by specialized heart-resident macrophages, altogether supporting proper heart function. PMID: 33027673 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Bartelt A, Weber C Tags: Cell Metab Source Type: research

Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids.
eacute;rez-Brocal V, Ricart W, Moya A, Fernández-Real X, Ramió-Torrentà L, Pamplona R, Sol J, Jové M, Portero-Otin M, Maldonado R, Fernández-Real JM Abstract The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids...
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, Contreras-Rodríguez O, Blasco G, Coll C, Biarnés C, Miranda-Olivos R, Latorre J, Moreno-Navarrete JM, Castells-Nobau A, Sabater M, Palomo-Buitrago ME, Puig J, Pedraza S, Gich J, Pérez-Brocal V, Ri Tags: Cell Metab Source Type: research

Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes.
We report that static magnetic and electric fields (sBE) noninvasively modulate the systemic GSH-to-GSSG redox couple to promote a healthier systemic redox environment that is reducing. Strikingly, when applied to mouse models of T2D, sBE rapidly ameliorates insulin resistance and glucose intolerance in as few as 3 days with no observed adverse effects. Scavenging paramagnetic byproducts of oxygen metabolism with SOD2 in hepatic mitochondria fully abolishes these insulin sensitizing effects, demonstrating that mitochondrial superoxide mediates induction of these therapeutic changes. Our findings introduce a remarkable...
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Carter CS, Huang SC, Searby CC, Cassaidy B, Miller MJ, Grzesik WJ, Piorczynski TB, Pak TK, Walsh SA, Acevedo M, Zhang Q, Mapuskar KA, Milne GL, Hinton AO, Guo DF, Weiss R, Bradberry K, Taylor EB, Rauckhorst AJ, Dick DW, Akurathi V, Falls-Hubert KC, Wagner Tags: Cell Metab Source Type: research

A2A Receptor Activation Attenuates Hypertensive Cardiac Remodeling via Promoting Brown Adipose Tissue-Derived FGF21.
PMID: 33027676 [PubMed] (Source: Cell Metabolism)
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Ruan CC, Kong LR, Chen XH, Ma Y, Pan XX, Zhang ZB, Gao PJ Tags: Cell Metab Source Type: research

Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.
ou M PMID: 33027677 [PubMed] (Source: Cell Metabolism)
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY, Chung ST, Costa E, Courville A, Darcey V, Fletcher LA, Forde CG, Gharib AM, Guo J, Howard R, Joseph PV, McGehee S, Ouwerkerk R, Raisinger K, Rozga I, Stagliano M, Walter M, Walter PJ, Yang S, Z Tags: Cell Metab Source Type: research

Retraction Notice to: The Cancer-Associated FGFR4-G388R Polymorphism Enhances Pancreatic Insulin Secretion and Modifies the Risk of Diabetes.
h A, Asa SL PMID: 33027678 [PubMed] (Source: Cell Metabolism)
Source: Cell Metabolism - October 6, 2020 Category: Cytology Authors: Ezzat S, Zheng L, Florez JC, Stefan N, Mayr T, Hliang MM, Jablonski K, Harden M, Stanĉáková A, Laakso M, Haring HU, Ullrich A, Asa SL Tags: Cell Metab Source Type: research

Ablation of Fat Cells in Adult Mice Induces Massive Bone Gain.
Abstract Adipocytes control bone mass, but the mechanism is unclear. To explore the effect of postnatal adipocyte elimination on bone cells, we mated mice expressing an inducible primate diphtheria toxin receptor (DTR) to those bearing adiponectin (ADQ)-Cre. DTR activation eliminates peripheral and marrow adipocytes in these DTRADQ mice. Within 4 days of DTR activation, the systemic bone mass of DTRADQ mice began to increase due to stimulated osteogenesis, with a 1,000% expansion by 10-14 days post-DTR treatment. This adipocyte ablation-mediated enhancement of skeletal mass reflected bone morphogenetic p...
Source: Cell Metabolism - October 3, 2020 Category: Cytology Authors: Zou W, Rohatgi N, Brestoff JR, Li Y, Barve RA, Tycksen E, Kim Y, Silva MJ, Teitelbaum SL Tags: Cell Metab Source Type: research

Immunometabolism in the Single-Cell Era.
Abstract Emerging research has identified metabolic pathways that are crucial for the proper regulation of immune cells and how, when deranged, they can cause immune dysfunction and disease progression. However, due to technical limitations such insights have relied heavily on bulk measurements in immune cells, often activated in vitro. But with the emergence of single-cell applications, researchers can now estimate the metabolic state of individual immune cells in clinical samples. Here, we review these single-cell techniques and their ability to validate common principles in immunometabolism, while also rev...
Source: Cell Metabolism - September 29, 2020 Category: Cytology Authors: Artyomov MN, Van den Bossche J Tags: Cell Metab Source Type: research

Insulin and Leptin/Upd2 Exert Opposing Influences on Synapse Number in Fat-Sensing Neurons.
Abstract Energy-sensing neural circuits decide to expend or conserve resources based, in part, on the tonic, steady-state, energy-store information they receive. Tonic signals, in the form of adipose tissue-derived adipokines, set the baseline level of activity in the energy-sensing neurons, thereby providing context for interpretation of additional inputs. However, the mechanism by which tonic adipokine information establishes steady-state neuronal function has heretofore been unclear. We show here that under conditions of nutrient surplus, Upd2, a Drosophila leptin ortholog, regulates actin-based synapse reorgan...
Source: Cell Metabolism - September 21, 2020 Category: Cytology Authors: Brent AE, Rajan A Tags: Cell Metab Source Type: research

Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy.
ov A, Dietmann S, Cavo M, Catani L, Curti A, Vázquez J, Frezza C, Huntly BJ, Schwaller J, Méndez-Ferrer S Abstract Like normal hematopoietic stem cells, leukemic stem cells depend on their bone marrow (BM) microenvironment for survival, but the underlying mechanisms remain largely unknown. We have studied the contribution of nestin+ BM mesenchymal stem cells (BMSCs) to MLL-AF9-driven acute myeloid leukemia (AML) development and chemoresistance in vivo. Unlike bulk stroma, nestin+ BMSC numbers are not reduced in AML, but their function changes to support AML cells, at the expense of non-mutated h...
Source: Cell Metabolism - September 15, 2020 Category: Cytology Authors: Forte D, García-Fernández M, Sánchez-Aguilera A, Stavropoulou V, Fielding C, Martín-Pérez D, López JA, Costa ASH, Tronci L, Nikitopoulou E, Barber M, Gallipoli P, Marando L, Fernández de Castillejo CL, Tzankov A, Dietmann S, Cavo M, Catani L, Curti Tags: Cell Metab Source Type: research

Quantitative Analysis of the Physiological Contributions of Glucose to the TCA Cycle.
Abstract The nutritional source for catabolism in the tricarboxylic acid (TCA) cycle is a fundamental question in metabolic physiology. Limited by data and mathematical analysis, controversy exists. Using isotope-labeling data in vivo across several experimental conditions, we construct multiple models of central carbon metabolism and develop methods based on metabolic flux analysis (MFA) to solve for the preferences of glucose, lactate, and other nutrients used in the TCA cycle. We show that in nearly all circumstances, glucose contributes more than lactate as a substrate to the TCA cycle. This conclusion is...
Source: Cell Metabolism - September 15, 2020 Category: Cytology Authors: Liu S, Dai Z, Cooper DE, Kirsch DG, Locasale JW Tags: Cell Metab Source Type: research

Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16high Cells In  Vivo.
Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16high Cells In Vivo. Cell Metab. 2020 Sep 11;: Authors: Omori S, Wang TW, Johmura Y, Kanai T, Nakano Y, Kido T, Susaki EA, Nakajima T, Shichino S, Ueha S, Ozawa M, Yokote K, Kumamoto S, Nishiyama A, Sakamoto T, Yamaguchi K, Hatakeyama S, Shimizu E, Katayama K, Yamada Y, Yamazaki S, Iwasaki K, Miyoshi C, Funato H, Yanagisawa M, Ueno H, Imoto S, Furukawa Y, Yoshida N, Matsushima K, Ueda HR, Miyajima A, Nakanishi M Abstract Cell senescence plays a key role in age-associated organ dysfunction, but the in vivo pathogenesi...
Source: Cell Metabolism - September 10, 2020 Category: Cytology Authors: Omori S, Wang TW, Johmura Y, Kanai T, Nakano Y, Kido T, Susaki EA, Nakajima T, Shichino S, Ueha S, Ozawa M, Yokote K, Kumamoto S, Nishiyama A, Sakamoto T, Yamaguchi K, Hatakeyama S, Shimizu E, Katayama K, Yamada Y, Yamazaki S, Iwasaki K, Miyoshi C, Funato Tags: Cell Metab Source Type: research

Shining Light on the COVID-19 Pandemic: A Vitamin D Receptor Checkpoint in Defense of Unregulated Wound Healing.
Abstract SARS-CoV-2 pneumonitis can quickly strike to incapacitate the lung, leading to severe disease and sometimes death. In this perspective, we suggest that vitamin D deficiency and the failure to activate the vitamin D receptor (VDR) can aggravate this respiratory syndrome by igniting a wounding response in stellate cells of the lung. The FDA-approved injectable vitamin D analog, paricalcitol, suppresses stellate cell-derived murine hepatic and pancreatic pro-inflammatory and pro-fibrotic changes. Therefore, we suggest a possible parallel program in the pulmonary stellate cells of COVID-19 patients and propos...
Source: Cell Metabolism - September 10, 2020 Category: Cytology Authors: Evans RM, Lippman SM Tags: Cell Metab Source Type: research

Obesity-Linked PPAR γ S273 Phosphorylation Promotes Insulin Resistance through Growth Differentiation Factor 3.
Obesity-Linked PPARγ S273 Phosphorylation Promotes Insulin Resistance through Growth Differentiation Factor 3. Cell Metab. 2020 Sep 11;: Authors: Hall JA, Ramachandran D, Roh HC, DiSpirito JR, Belchior T, Zushin PH, Palmer C, Hong S, Mina AI, Liu B, Deng Z, Aryal P, Jacobs C, Tenen D, Brown CW, Charles JF, Shulman GI, Kahn BB, Tsai LTY, Rosen ED, Spiegelman BM, Banks AS Abstract The thiazolidinediones (TZDs) are ligands of PPARγ that improve insulin sensitivity, but their use is limited by significant side effects. Recently, we demonstrated a mechanism wherein TZDs improve insulin sensitiv...
Source: Cell Metabolism - September 10, 2020 Category: Cytology Authors: Hall JA, Ramachandran D, Roh HC, DiSpirito JR, Belchior T, Zushin PH, Palmer C, Hong S, Mina AI, Liu B, Deng Z, Aryal P, Jacobs C, Tenen D, Brown CW, Charles JF, Shulman GI, Kahn BB, Tsai LTY, Rosen ED, Spiegelman BM, Banks AS Tags: Cell Metab Source Type: research

Warmth Prevents Bone Loss Through the Gut Microbiota.
t N, Trajkovski M Abstract Osteoporosis is the most prevalent metabolic bone disease, characterized by low bone mass and microarchitectural deterioration. Here, we show that warmth exposure (34°C) protects against ovariectomy-induced bone loss by increasing trabecular bone volume, connectivity density, and thickness, leading to improved biomechanical bone strength in adult female, as well as in young male mice. Transplantation of the warm-adapted microbiota phenocopies the warmth-induced bone effects. Both warmth and warm microbiota transplantation revert the ovariectomy-induced transcriptomics changes of the ...
Source: Cell Metabolism - September 9, 2020 Category: Cytology Authors: Chevalier C, Kieser S, Çolakoğlu M, Hadadi N, Brun J, Rigo D, Suárez-Zamorano N, Spiljar M, Fabbiano S, Busse B, Ivanišević J, Macpherson A, Bonnet N, Trajkovski M Tags: Cell Metab Source Type: research

Microenvironmental Aspartate Preserves Leukemic Cells from Therapy-Induced Metabolic Collapse.
Abstract Metabolic dialogue between tumors and their microenvironment emerges as a key regulator of chemoresistance, the major barrier for the treatment of several cancers. In this issue of Cell Metabolism, van Gastel et al. decipher the pivotal role of stromal glutamine-derived aspartate to sustain pyrimidine biosynthesis in chemoresistant acute myeloid leukemia (AML) and thus state it as a target for anti-cancer therapy. PMID: 32877685 [PubMed - as supplied by publisher] (Source: Cell Metabolism)
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Stuani L, Sarry JE Tags: Cell Metab Source Type: research

Alpha-Ketoglutarate, the Metabolite that Regulates Aging in Mice.
Abstract In this issue of Cell Metabolism, Asadi Shahmirzadi et al. (2020) demonstrate that late-onset dietary supplementation with calcium alpha-ketoglutarate results in increased survival, compressed morbidity, and reduced frailty in mice. The study provides further evidence for critical links between metabolism, inflammation, and aging. PMID: 32877686 [PubMed - as supplied by publisher] (Source: Cell Metabolism)
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Rhoads TW, Anderson RM Tags: Cell Metab Source Type: research

A Complex Acetate-ment: Timing of Exposure Determines Memory T Cell Fate.
Abstract In this issue of Cell Metabolism, Balmer et al. show that the timing and concentration of acetate exposure is critical to how it is metabolized by and affects the function of CD8 T cells. When abundantly present at the time of reactivation, acetate rewires CD8 T cell metabolism to suppress their reactivation and limit inflammation. PMID: 32877687 [PubMed - as supplied by publisher] (Source: Cell Metabolism)
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Heieis GA, Everts B Tags: Cell Metab Source Type: research

Not Chopped Liver-A Careful, Fate-Mapping Study of Macrophages in NASH.
Abstract Macrophages are central to the pathogenesis of non-alcoholic steatohepatitis (NASH). However, the identities and functional relationships between tissue-resident and tissue-recruited macrophages in NASH remain poorly understood. A recent study from Seidman et al. (2020) elucidates, at single-cell resolution, the fates, niches, and regulatory landscapes of liver tissue-resident and tissue-recruited macrophage populations in NASH. PMID: 32877688 [PubMed - as supplied by publisher] (Source: Cell Metabolism)
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Moreno-Fernandez ME, Miraldi ER, Divanovic S Tags: Cell Metab Source Type: research

An Antibody Attack against Body Wasting in Cancer.
Abstract Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals. PMID: 32877689 [PubMed - as supplied by publisher] (Source: Cell Metabolism)
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Rohm M, Herzig S Tags: Cell Metab Source Type: research

Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.
Abstract Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines. We pr...
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Asadi Shahmirzadi A, Edgar D, Liao CY, Hsu YM, Lucanic M, Asadi Shahmirzadi A, Wiley CD, Gan G, Kim DE, Kasler HG, Kuehnemann C, Kaplowitz B, Bhaumik D, Riley RR, Kennedy BK, Lithgow GJ Tags: Cell Metab Source Type: research

A High-Density Human Mitochondrial Proximity Interaction Network.
Abstract We used BioID, a proximity-dependent biotinylation assay with 100 mitochondrial baits from all mitochondrial sub-compartments, to create a high-resolution human mitochondrial proximity interaction network. We identified 1,465 proteins, producing 15,626 unique high-confidence proximity interactions. Of these, 528 proteins were previously annotated as mitochondrial, nearly half of the mitochondrial proteome defined by Mitocarta 2.0. Bait-bait analysis showed a clear separation of mitochondrial compartments, and correlation analysis among preys across all baits allowed us to identify functional clusters invo...
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Antonicka H, Lin ZY, Janer A, Aaltonen MJ, Weraarpachai W, Gingras AC, Shoubridge EA Tags: Cell Metab Source Type: research

Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1 α/Glycolysis-Dependent Axis.
Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis. Cell Metab. 2020 Sep 01;32(3):498-499 Authors: Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, de Biagi Junior CAO, Crunfli F, Jimenez Restrepo JL, Vendramini PH, Reis-de-Oliveira G, Bispo Dos Santos K, Toledo-Teixeira DA, Parise PL, Martini MC, Marques RE, Carmo HR, Borin A, Coimbra LD, Boldrini VO, Brunetti NS, Vieira AS, Mansour E, Ulaf RG, Bernardes AF, Nunes TA, Ribeiro LC, Palma AC, Agrela MV, Moretti ML, Sposito AC, Pereira...
Source: Cell Metabolism - August 31, 2020 Category: Cytology Authors: Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, de Biagi Junior CAO, Crunfli F, Jimenez Restrepo JL, Vendramini PH, Reis-de-Oliveira G, Bispo Dos Santos K, Toledo-Teixeira DA, Parise PL, Martini Tags: Cell Metab Source Type: research

Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes.
i YX, Li H Abstract The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particular...
Source: Cell Metabolism - August 19, 2020 Category: Cytology Authors: Cheng X, Liu YM, Li H, Zhang X, Lei F, Qin JJ, Chen Z, Deng KQ, Lin L, Chen MM, Song X, Xia M, Huang X, Liu W, Cai J, Zhang XJ, Zhou F, Zhang P, Wang Y, Ma X, Xu Q, Yang J, Ye P, Mao W, Huang X, Xia J, Zhang BH, Guo J, Zhu L, Lu Z, Yuan Y, Wei X, She ZG, Tags: Cell Metab Source Type: research

The Role of HIF in Immunity and Inflammation.
Abstract HIF is a transcription factor that plays an essential role in the cellular response to low oxygen, orchestrating a metabolic switch that allows cells to survive in this environment. In immunity, infected and inflamed tissues are often hypoxic, and HIF helps immune cells adapt. HIF-α stabilization can also occur under normoxia during immunity and inflammation, where it regulates metabolism but in addition can directly regulate expression of immune genes. Here we review the role of HIF in immunity, including its role in macrophages, dendritic cells, neutrophils, T cells, and B cells. Its role in ...
Source: Cell Metabolism - August 18, 2020 Category: Cytology Authors: McGettrick AF, O'Neill LAJ Tags: Cell Metab Source Type: research

Triose Kinase Controls the Lipogenic Potential of Fructose and Dietary Tolerance.
Abstract The surge in fructose consumption is a major factor behind the rapid rise of nonalcoholic fatty liver disease in modern society. Through flux and genetic analyses, we demonstrate that fructose is catabolized at a much higher rate than glucose, and triose kinase (TK) couples fructolysis with lipogenesis metabolically and transcriptionally. In the absence of TK, fructose oxidation is accelerated through the activation of aldehyde dehydrogenase (ALDH) and serine biosynthesis, accompanied by increased oxidative stress and fructose aversion. TK is also required by the endogenous fructolysis pathway to drive li...
Source: Cell Metabolism - August 10, 2020 Category: Cytology Authors: Liu L, Li T, Liao Y, Wang Y, Gao Y, Hu H, Huang H, Wu F, Chen YG, Xu S, Fu S Tags: Cell Metab Source Type: research

Quantitative Fluxomics of Circulating Metabolites.
Abstract Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting for both circulatory metabolic cycles and tissue TCA inputs, across fed and fasted...
Source: Cell Metabolism - August 9, 2020 Category: Cytology Authors: Hui S, Cowan AJ, Zeng X, Yang L, TeSlaa T, Li X, Bartman C, Zhang Z, Jang C, Wang L, Lu W, Rojas J, Baur J, Rabinowitz JD Tags: Cell Metab Source Type: research

The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation.
Abstract The Krebs cycle-derived metabolite itaconate is highly upregulated in inflammatory macrophages and exerts immunomodulatory effects through cysteine modifications on target proteins. The NLRP3 inflammasome, which cleaves IL-1β, IL-18, and gasdermin D, must be tightly regulated to avoid excessive inflammation. Here we provide evidence that itaconate modifies NLRP3 and inhibits inflammasome activation. Itaconate and its derivative, 4-octyl itaconate (4-OI), inhibited NLRP3 inflammasome activation, but not AIM2 or NLRC4. Conversely, NLRP3 activation was increased in itaconate-depleted Irg1-/- macrophages...
Source: Cell Metabolism - August 3, 2020 Category: Cytology Authors: Hooftman A, Angiari S, Hester S, Corcoran SE, Runtsch MC, Ling C, Ruzek MC, Slivka PF, McGettrick AF, Banahan K, Hughes MM, Irvine AD, Fischer R, O'Neill LAJ Tags: Cell Metab Source Type: research

Untangling iNKT Cell Function in Adipose Tissue Homeostasis.
Abstract iNKT cells are important regulatory cells in metabolic health and disease. In this issue of Cell Metabolism, LaMarche et al. (2020) clarify the origin and heterogeneity of these unconventional T cells and identify the specific signals in adipose tissues that direct their function. PMID: 32755605 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - August 3, 2020 Category: Cytology Authors: Franklin RA, Medzhitov R Tags: Cell Metab Source Type: research

A Vectorial, ER-Mitochondria Link to Energy Homeostasis in the Vascular Endothelium.
Abstract The precise mechanisms of free fatty acid (FFA) uptake in the vascular endothelium are unclear. In this issue of Cell Metabolism, Ibrahim et al. (2020) discover that FFA uptake is partially mediated by a vectorial, ER-mitochondria link, in which mitochondrial ATP production is locally used for the acyl-CoA synthetase activity of the ER-located fatty acid transport protein 4. PMID: 32755606 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - August 3, 2020 Category: Cytology Authors: Boutagy NE, Fowler JW, Sessa WC Tags: Cell Metab Source Type: research

The Link between Stress and IL-6 Is Heating Up.
Abstract Psychological stress has long been known to reduce adaptability to inflammatory challenges, although the precise mechanism has remained elusive. In a recent issue of Cell, Qing et al. (2020) demonstrate that psychological stress induces secretion of IL-6 from brown adipose tissue, which promotes hepatic gluconeogenesis, and reduces host fitness to inflammatory insults. PMID: 32755607 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - August 3, 2020 Category: Cytology Authors: Darcy J, Tseng YH Tags: Cell Metab Source Type: research

Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation.
Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation. Cell Metab. 2020 Aug 04;32(2):287-300.e7 Authors: Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, Jespersen NZ, Kooijman S, Boon MR, Fortin M, Phoenix S, Frisch F, Guérin B, Turcotte ÉE, Haman F, Richard D, Picard F, Rensen PCN, Scheele C, Carpentier AC Abstract Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β3-adrenergic receptor (β3-AR), the adrenergic recep...
Source: Cell Metabolism - August 3, 2020 Category: Cytology Authors: Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, Jespersen NZ, Kooijman S, Boon MR, Fortin M, Phoenix S, Frisch F, Guérin B, Turcotte ÉE, Haman F, Richard D, Picard F, Rensen PCN, Scheele C, Carpentier AC Tags: Cell Metab Source Type: research

Sirt2 Inhibition Enhances Metabolic Fitness and Effector Functions of Tumor-Reactive T Cells.
Kim S Abstract Dysregulated metabolism is a key driver of maladaptive tumor-reactive T lymphocytes within the tumor microenvironment. Actionable targets that rescue the effector activity of antitumor T cells remain elusive. Here, we report that the Sirtuin-2 (Sirt2) NAD+-dependent deacetylase inhibits T cell metabolism and impairs T cell effector functions. Remarkably, upregulation of Sirt2 in human tumor-infiltrating lymphocytes (TILs) negatively correlates with response to TIL therapy in advanced non-small-cell lung cancer. Mechanistically, Sirt2 suppresses T cell metabolism by targeting key ...
Source: Cell Metabolism - July 30, 2020 Category: Cytology Authors: Hamaidi I, Zhang L, Kim N, Wang MH, Iclozan C, Fang B, Liu M, Koomen JM, Berglund AE, Yoder SJ, Yao J, Engelman RW, Creelan BC, Conejo-Garcia JR, Antonia SJ, Mulé JJ, Kim S Tags: Cell Metab Source Type: research

Induction of a Timed Metabolic Collapse to Overcome Cancer Chemoresistance.
Abstract Cancer relapse begins when malignant cells pass through the extreme metabolic bottleneck of stress from chemotherapy and the byproducts of the massive cell death in the surrounding region. In acute myeloid leukemia, complete remissions are common, but few are cured. We tracked leukemia cells in vivo, defined the moment of maximal response following chemotherapy, captured persisting cells, and conducted unbiased metabolomics, revealing a metabolite profile distinct from the pre-chemo growth or post-chemo relapse phase. Persisting cells used glutamine in a distinctive manner, preferentially fueling pyr...
Source: Cell Metabolism - July 29, 2020 Category: Cytology Authors: van Gastel N, Spinelli JB, Sharda A, Schajnovitz A, Baryawno N, Rhee C, Oki T, Grace E, Soled HJ, Milosevic J, Sykes DB, Hsu PP, Vander Heiden MG, Vidoudez C, Trauger SA, Haigis MC, Scadden DT Tags: Cell Metab Source Type: research

Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.
S, Jones RG, Hess C Abstract Serum acetate increases upon systemic infection. Acutely, assimilation of acetate expands the capacity of memory CD8+ T cells to produce IFN-γ. Whether acetate modulates memory CD8+ T cell metabolism and function during pathogen re-encounter remains unexplored. Here we show that at sites of infection, high acetate concentrations are being reached, yet memory CD8+ T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, being thus largely excluded from incorporation into cellular metabolic pathways, now had different effects, namely (1) directly...
Source: Cell Metabolism - July 23, 2020 Category: Cytology Authors: Balmer ML, Ma EH, Thompson A, Epple R, Unterstab G, Lötscher J, Dehio P, Schürch CM, Warncke JD, Perrin G, Woischnig AK, Grählert J, Löliger J, Assmann N, Bantug GR, Schären OP, Khanna N, Egli A, Bubendorf L, Rentsch K, Hapfelmeier S, Jones RG, Hess Tags: Cell Metab Source Type: research

Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity.
Abstract Regulatory T cells (Tregs) are vital for the maintenance of immune homeostasis, while their dysfunction constitutes a cardinal feature of autoimmunity. Under steady-state conditions, mitochondrial metabolism is critical for Treg function; however, the metabolic adaptations of Tregs during autoimmunity are ill-defined. Herein, we report that elevated mitochondrial oxidative stress and a robust DNA damage response (DDR) associated with cell death occur in Tregs in individuals with autoimmunity. In an experimental autoimmune encephalitis (EAE) mouse model of autoimmunity, we found a Treg dysfunction rec...
Source: Cell Metabolism - July 21, 2020 Category: Cytology Authors: Alissafi T, Kalafati L, Lazari M, Filia A, Kloukina I, Manifava M, Lim JH, Alexaki VI, Ktistakis NT, Doskas T, Garinis GA, Chavakis T, Boumpas DT, Verginis P Tags: Cell Metab Source Type: research

Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP Expression and Glucagon Action.
Abstract Diabetes is characterized by hyperglycemia, loss of functional islet beta cell mass, deficiency of glucose-lowering insulin, and persistent alpha cell secretion of gluconeogenic glucagon. Still, no therapies that target these underlying processes are available. We therefore performed high-throughput screening of 300,000 compounds and extensive medicinal chemistry optimization and here report the discovery of SRI-37330, an orally bioavailable, non-toxic small molecule, which effectively rescued mice from streptozotocin- and obesity-induced (db/db) diabetes. Interestingly, in rat cells and in mouse and huma...
Source: Cell Metabolism - July 21, 2020 Category: Cytology Authors: Thielen LA, Chen J, Jing G, Moukha-Chafiq O, Xu G, Jo S, Grayson TB, Lu B, Li P, Augelli-Szafran CE, Suto MJ, Kanke M, Sethupathy P, Kim JK, Shalev A Tags: Cell Metab Source Type: research

SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition.
Abstract SGLT2 inhibitors offer strong renoprotection in subjects with diabetic kidney disease (DKD). But the mechanism for such protection is not clear. Here, we report that in damaged proximal tubules of high-fat diet-fed ApoE-knockout mice, a model of non-proteinuric DKD, ATP production shifted from lipolysis to ketolysis dependent due to hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). We further found that empagliflozin raised endogenous ketone body (KB) levels, and thus its use or treatment with 1,3-butanediol, a KB precursor, prevented decreases in renal ATP levels and organ damage...
Source: Cell Metabolism - July 18, 2020 Category: Cytology Authors: Tomita I, Kume S, Sugahara S, Osawa N, Yamahara K, Yasuda-Yamahara M, Takeda N, Chin-Kanasaki M, Kaneko T, Mayoux E, Mark M, Yanagita M, Ogita H, Araki SI, Maegawa H Tags: Cell Metab Source Type: research

Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1 α/Glycolysis-Dependent Axis.
Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis. Cell Metab. 2020 Jul 17;: Authors: Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, de Biagi Junior CAO, Crunfli F, Jimenez Restrepo JL, Vendramini PH, Reis-de-Oliveira G, Bispo Dos Santos K, Toledo-Teixeira DA, Parise PL, Martini MC, Marques RE, Carmo HR, Borin A, Coimbra LD, Boldrini VO, Brunetti NS, Vieira AS, Mansour E, Ulaf RG, Bernardes AF, Nunes TA, Ribeiro LC, Palma AC, Agrela MV, Moretti ML, Sposito AC, Pereira FB, Velloso...
Source: Cell Metabolism - July 16, 2020 Category: Cytology Authors: Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, de Biagi Junior CAO, Crunfli F, Jimenez Restrepo JL, Vendramini PH, Reis-de-Oliveira G, Bispo Dos Santos K, Toledo-Teixeira DA, Parise PL, Martini Tags: Cell Metab Source Type: research

PHD3 Loss Promotes Exercise Capacity and Fat Oxidation in Skeletal Muscle.
Abstract Rapid alterations in cellular metabolism allow tissues to maintain homeostasis during changes in energy availability. The central metabolic regulator acetyl-CoA carboxylase 2 (ACC2) is robustly phosphorylated during cellular energy stress by AMP-activated protein kinase (AMPK) to relieve its suppression of fat oxidation. While ACC2 can also be hydroxylated by prolyl hydroxylase 3 (PHD3), the physiological consequence thereof is poorly understood. We find that ACC2 phosphorylation and hydroxylation occur in an inverse fashion. ACC2 hydroxylation occurs in conditions of high energy and represses fatty acid ...
Source: Cell Metabolism - July 8, 2020 Category: Cytology Authors: Yoon H, Spinelli JB, Zaganjor E, Wong SJ, German NJ, Randall EC, Dean A, Clermont A, Paulo JA, Garcia D, Li H, Rombold O, Agar NYR, Goodyear LJ, Shaw RJ, Gygi SP, Auwerx J, Haigis MC Tags: Cell Metab Source Type: research

Large-Scale Proteomics Highlights Glial Role in Neurodegeneration.
Abstract Recent quantitative mass spectrometry and coexpression network analysis of postmortem human brain samples identified protein networks responsible for sugar metabolism and function of astrocytes and microglia are altered in Alzheimer's disease and other types of neurodegenerative disorders. Boosting neuroglial function may represent a new strategy for containing neurodegeneration. PMID: 32640242 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - July 6, 2020 Category: Cytology Authors: Verkhratsky A, Zorec R Tags: Cell Metab Source Type: research

SGLT2 Inhibitor: Not a Traditional Diuretic for Heart Failure.
Abstract Recent studies have shown impressive cardiovascular health benefits in individuals treated with SGLT2 inhibitors (SGLT2i) regardless of diabetic status. The underlying mechanisms driving these benefits are not well understood. Recently in Circulation, Griffin et al. (2020) reported the first human study investigating the diuretic effect of empagliflozin. PMID: 32640243 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - July 6, 2020 Category: Cytology Authors: Verma A, Patel AB, Waikar SS Tags: Cell Metab Source Type: research

Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy.
ainen A PMID: 32640244 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - July 6, 2020 Category: Cytology Authors: Pirinen E, Auranen M, Khan NA, Brilhante V, Urho N, Pessia A, Hakkarainen A, Ulla Heinonen JK, Schmidt MS, Haimilahti K, Piirilä P, Lundbom N, Taskinen MR, Brenner C, Velagapudi V, Pietiläinen KH, Suomalainen A Tags: Cell Metab Source Type: research

The World Goes Bats: Living Longer and Tolerating Viruses.
Abstract For centuries, people believed that bats possessed sinister powers. Bats are thought to be ancestral hosts to many deadly viruses affecting humans including Ebola, rabies, and most recently SARS-CoV-2 coronavirus. However, bats themselves tolerate these viruses without ill effects. The second power that bats have is their longevity. Bats live much longer than similar-sized land mammals. Here we review how bats' ability to control inflammation may be contributing to their longevity. The underlying mechanisms may hold clues to developing new treatments for age-related diseases. Now may be the time to use sc...
Source: Cell Metabolism - July 6, 2020 Category: Cytology Authors: Gorbunova V, Seluanov A, Kennedy BK Tags: Cell Metab Source Type: research

Finding the Sweet Spot: Parsing Tissue-Specific Contributions of Fructose Metabolism.
Abstract The abundance of dietary sweeteners and overconsumption of fructose are widely thought to promote metabolic disease. In this issue of Cell Metabolism, Andres-Hernando et al. (2020) identify the liver as the major site of fructose metabolism-mediated metabolic dysfunction and identify a surprising role for intestinal fructose metabolism in driving fructose intake. PMID: 32640246 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - July 6, 2020 Category: Cytology Authors: Tesz GJ, Bence KK Tags: Cell Metab Source Type: research

Constitutional Thinness: tALKing the tALK or wALKing the wALK?
Abstract In a recent issue of Cell, Orthofer et al. (2020) present a body of data from mice, flies, and humans that suggest (1) a physiological role for Alk in the normal control of energy balance across several species and (2) a possible contribution of genetic variants in or near ALK to the variability of adiposity in humans, more specifically at its lower end. PMID: 32640247 [PubMed - in process] (Source: Cell Metabolism)
Source: Cell Metabolism - July 6, 2020 Category: Cytology Authors: Tung YCL, O'Rahilly S Tags: Cell Metab Source Type: research

FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake.
Abstract Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central targets mediating these effects have been unclear. Here, we identify FGF21 target cells in the hypothalamus and reveal that FGF21 signaling to glutamatergic neurons is both necessary and sufficient to mediate FGF21-induced sugar suppression and sweet-taste preference. Moreover, we show that FGF21 acts directly...
Source: Cell Metabolism - June 29, 2020 Category: Cytology Authors: Jensen-Cody SO, Flippo KH, Claflin KE, Yavuz Y, Sapouckey SA, Walters GC, Usachev YM, Atasoy D, Gillum MP, Potthoff MJ Tags: Cell Metab Source Type: research