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Cell Metabolism

Kyung Hwa Kim, Jyung Mean Son, Bérénice A Benayoun, Changhan Lee
Cellular homeostasis is coordinated through communication between mitochondria and the nucleus, organelles that each possess their own genomes. Whereas the mitochondrial genome is regulated by factors encoded in the nucleus, the nuclear genome is currently not known to be actively controlled by factors encoded in the mitochondrial DNA. Here, we show that MOTS-c, a peptide encoded in the mitochondrial genome, translocates to the nucleus and regulates nuclear gene expression following metabolic stress in a 5'-adenosine monophosphate-activated protein kinase (AMPK)-dependent manner...
June 27, 2018: Cell Metabolism
Gantsetseg Tumurkhuu, Jargalsaikhan Dagvadorj, Rebecca A Porritt, Timothy R Crother, Kenichi Shimada, Elizabeth J Tarling, Ebru Erbay, Moshe Arditi, Shuang Chen
Pathogen burden accelerates atherosclerosis, but the mechanisms remain unresolved. Activation of the NLRP3 inflammasome is linked to atherogenesis. Here we investigated whether Chlamydia pneumoniae ( infection engages NLRP3 in promoting atherosclerosis. potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr-/- mice. acceleration of atherosclerosis was significantly dependent on NLRP3 and caspase-1. We discovered that C...
June 18, 2018: Cell Metabolism
Layla Kamareddine, William P Robins, Cristin D Berkey, John J Mekalanos, Paula I Watnick
Enteroendocrine cells (EEs) are interspersed between enterocytes and stem cells in the Drosophila intestinal epithelium. Like enterocytes, EEs express components of the immune deficiency (IMD) innate immune pathway, which activates transcription of genes encoding antimicrobial peptides. The discovery of large lipid droplets in intestines of IMD pathway mutants prompted us to investigate the role of the IMD pathway in the host metabolic response to its intestinal microbiota. Here we provide evidence that the short-chain fatty acid acetate is a microbial metabolic signal that activates signaling through the enteroendocrine IMD pathway in a PGRP-LC-dependent manner...
June 15, 2018: Cell Metabolism
Elsa Pflimlin, Maximilian Bielohuby, Marcus Korn, Kristin Breitschopf, Matthias Löhn, Paulus Wohlfart, Anish Konkar, Michael Podeschwa, Felix Bärenz, Anja Pfenninger, Uwe Schwahn, Till Opatz, Marcel Reimann, Stefan Petry, Norbert Tennagels
Fatty acid esters of hydroxylated fatty acids (FAHFAs) were discovered as a novel class of endogenous mammalian lipids whose profound effects on metabolism have been shown. In the current study, in vitro and in vivo the metabolic effects of two of these FAHFAs, namely palmitic acid-5- (or -9) -hydroxy-stearic acid (5- or 9-PAHSA, respectively) were profiled. In DIO mice fed with differentially composed low- or high-fat diets, acute and subchronic treatment with 5-PAHSA and 9-PAHSA alone, or in combination, did not significantly improve the deranged metabolic status...
June 15, 2018: Cell Metabolism
Yann Ravussin, Ethan Edwin, Molly Gallop, Lumei Xu, Alberto Bartolomé, Michael J Kraakman, Charles A LeDuc, Anthony W Ferrante
Weight is defended so that increases or decreases in body mass elicit responses that favor restoration of one's previous weight. While much is known about the signals that respond to weight loss and the central role that leptin plays, the lack of experimental systems studying the overfed state has meant little is known about pathways defending against weight gain. We developed a system to study this physiology and found that overfed mice defend against increased weight gain with graded anorexia but, unlike weight loss, this response is independent of circulating leptin concentration...
June 14, 2018: Cell Metabolism
Miriam Toledo, Ana Batista-Gonzalez, Emilio Merheb, Marie Louise Aoun, Elena Tarabra, Daorong Feng, Jaakko Sarparanta, Paola Merlo, Francesco Botrè, Gary J Schwartz, Jeffrey E Pessin, Rajat Singh
The circadian clock coordinates behavioral and circadian cues with availability and utilization of nutrients. Proteasomal degradation of clock repressors, such as cryptochrome (CRY)1, maintains periodicity. Whether macroautophagy, a quality control pathway, degrades circadian proteins remains unknown. Here we show that circadian proteins BMAL1, CLOCK, REV-ERBα, and CRY1 are lysosomal targets, and that macroautophagy affects the circadian clock by selectively degrading CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that CRY1 degradation is time-imprinted to maintenance of blood glucose...
June 11, 2018: Cell Metabolism
Rayanne B Burl, Vanesa D Ramseyer, Elizabeth A Rondini, Roger Pique-Regi, Yun-Hee Lee, James G Granneman
Recruitment of brown/beige adipocytes (BAs) in white adipose tissue (WAT) involves proliferation and differentiation of adipocyte stem cells (ASCs) in concert with close interactions with resident immune cells. To deconvolve stromal cell heterogeneity in a comprehensive and unbiased fashion, we performed single-cell RNA sequencing (scRNA-seq) of >33,000 stromal/vascular cells from epididymal WAT (eWAT) and inguinal WAT (iWAT) under control conditions and during β3-adrenergic receptor (ADRB3) activation...
June 9, 2018: Cell Metabolism
Justin G Fedor, Judy Hirst
Mitochondrial respiratory supercomplexes, comprising complexes I, III, and IV, are the minimal functional units of the electron transport chain. Assembling the individual complexes into supercomplexes may stabilize them, provide greater spatiotemporal control of respiration, or, controversially, confer kinetic advantages through the sequestration of local quinone and cytochrome c pools (substrate channeling). Here, we have incorporated an alternative quinol oxidase (AOX) into mammalian heart mitochondrial membranes to introduce a competing pathway for quinol oxidation and test for channeling...
June 9, 2018: Cell Metabolism
Qiong A Wang, Anying Song, Wanze Chen, Petra C Schwalie, Fang Zhang, Lavanya Vishvanath, Lei Jiang, Risheng Ye, Mengle Shao, Caroline Tao, Rana K Gupta, Bart Deplancke, Philipp E Scherer
Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. The fate of the original adipocytes during lactation and the developmental origin of the re-appearing adipocyte post involution are unclear. Here, we reveal that adipocytes in the mammary gland de-differentiate into Pdgfrα+ preadipocyte- and fibroblast-like cells during pregnancy and remain de-differentiated during lactation...
June 8, 2018: Cell Metabolism
Guang Lin, Pei-Tseng Lee, Kuchuan Chen, Dongxue Mao, Kai Li Tan, Zhongyuan Zuo, Wen-Wen Lin, Liping Wang, Hugo J Bellen
Mutations in PLA2G6 (PARK14) cause neurodegenerative disorders in humans, including autosomal recessive neuroaxonal dystrophy and early-onset parkinsonism. We show that loss of iPLA2-VIA, the fly homolog of PLA2G6, reduces lifespan, impairs synaptic transmission, and causes neurodegeneration. Phospholipases typically hydrolyze glycerol phospholipids, but loss of iPLA2-VIA does not affect the phospholipid composition of brain tissue but rather causes an elevation in ceramides. Reducing ceramides with drugs, including myriocin or desipramine, alleviates lysosomal stress and suppresses neurodegeneration...
June 7, 2018: Cell Metabolism
Mueez U Din, Teemu Saari, Juho Raiko, Nobu Kudomi, Stefanie F Maurer, Minna Lahesmaa, Tobias Fromme, Ez-Zoubir Amri, Martin Klingenspor, Olof Solin, Pirjo Nuutila, Kirsi A Virtanen
Human studies suggest that a meal elevates glucose uptake in brown adipose tissue (BAT). However, in postprandial state the thermogenic activity and the metabolism of non-esterified fatty acids (NEFAs) in BAT remain unclear. Using indirect calorimetry combined with positron emission tomography and computed tomography (PET/CT), we showed that whole-body and BAT thermogenesis (oxygen consumption) increases after the ingestion of a mixed carbohydrate-rich meal, to the same extent as in cold stress. Postprandial NEFA uptake into BAT is minimal, possibly due to elevated plasma insulin inhibiting lipolysis...
June 6, 2018: Cell Metabolism
Sara Della Torre, Nico Mitro, Clara Meda, Federica Lolli, Silvia Pedretti, Matteo Barcella, Luisa Ottobrini, Daniel Metzger, Donatella Caruso, Adriana Maggi
Sex impacts on liver physiology with severe consequences for energy metabolism and response to xenobiotic, hepatic, and extra-hepatic diseases. The comprehension of the biology subtending sex-related hepatic differences is therefore very relevant in the medical, pharmacological, and dietary perspective. The extensive application of metabolomics paired to transcriptomics here shows that, in the case of short-term fasting, the decision to maintain lipid synthesis using amino acids (aa) as a source of fuel is the key discriminant for the hepatic metabolism of male and female mice...
June 6, 2018: Cell Metabolism
Alexandra G DiFeliceantonio, Géraldine Coppin, Lionel Rigoux, Sharmili Edwin Thanarajah, Alain Dagher, Marc Tittgemeyer, Dana M Small
Post-ingestive signals conveying information about the nutritive properties of food are critical for regulating ingestive behavior. Here, using an auction task concomitant to fMRI scanning, we demonstrate that participants are willing to pay more for fat + carbohydrate compared with equally familiar, liked, and caloric fat or carbohydrate foods and that this potentiated reward is associated with response in areas critical for reward valuation, including the dorsal striatum and mediodorsal thalamus. We also show that individuals are better able to estimate the energy density of fat compared with carbohydrate and fat + carbohydrate foods, an effect associated with functional connectivity between visual (fusiform gyrus) and valuation (ventromedial prefrontal cortex) areas...
June 6, 2018: Cell Metabolism
Tsadik Habtetsion, Zhi-Chun Ding, Wenhu Pi, Tao Li, Chunwan Lu, Tingting Chen, Caixia Xi, Helena Spartz, Kebin Liu, Zhonglin Hao, Nahid Mivechi, Yuqing Huo, Bruce R Blazar, David H Munn, Gang Zhou
The inhibitory effects of cancer on T cell metabolism have been well established, but the metabolic impact of immunotherapy on tumor cells is poorly understood. Here, we developed a CD4+ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, we show that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species (ROS) in tumor cells...
May 30, 2018: Cell Metabolism
Ignacio Arias-Mayenco, Patricia González-Rodríguez, Hortensia Torres-Torrelo, Lin Gao, M Carmen Fernández-Agüera, Victoria Bonilla-Henao, Patricia Ortega-Sáenz, José López-Barneo
Acute O2 sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O2 -sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O2 -sensitive cells have unique metabolic characteristics that favor the hypoxic generation of mitochondrial complex I (MCI) signaling molecules, NADH and reactive oxygen species (ROS), which modulate membrane ion channels. We show that responsiveness to hypoxia progressively disappears after inducible deletion of the Ndufs2 gene, which encodes the 49 kDa subunit forming the coenzyme Q binding site in MCI, even in the presence of MCII substrates and chemical NAD+ regeneration...
May 28, 2018: Cell Metabolism
Jon O Lundberg, Mattias Carlström, Eddie Weitzberg
Nitric oxide (NO), generated from L-arginine and oxygen by NO synthases, is a pleiotropic signaling molecule involved in cardiovascular and metabolic regulation. More recently, an alternative pathway for the formation of this free radical has been explored. The inorganic anions nitrate (NO3 - ) and nitrite (NO2 - ), originating from dietary and endogenous sources, generate NO bioactivity in a process involving seemingly symbiotic oral bacteria and host enzymes in blood and tissues. The described cardio-metabolic effects of dietary nitrate from experimental and clinical studies include lowering of blood pressure, improved endothelial function, increased exercise performance, and reversal of metabolic syndrome, as well as antidiabetic effects...
July 3, 2018: Cell Metabolism
Hong Jiang, Jens C Brüning
In contrast to synaptic transmission, the mechanism of volume transmission-in which neurotransmitters or neuropeptides diffuse to many effector cells-is not extensively investigated, although it represents an important mode of neuronal communication. In this issue of Cell Metabolism, Noble et al. (2018) demonstrate how the orexigenic melanin-concentrating hormone (MCH) controls feeding behavior through cerebrospinal fluid (CSF) volume transmission.
July 3, 2018: Cell Metabolism
Ming Luo, Li Shang, Michael D Brooks, Evelyn Jiagge, Yongyou Zhu, Johanna M Buschhaus, Sarah Conley, Melissa A Fath, April Davis, Elizabeth Gheordunescu, Yongfang Wang, Ramdane Harouaka, Ann Lozier, Daniel Triner, Sean McDermott, Sofia D Merajver, Gary D Luker, Douglas R Spitz, Max S Wicha
Although breast cancer stem cells (BCSCs) display plasticity transitioning between quiescent mesenchymal-like (M) and proliferative epithelial-like (E) states, how this plasticity is regulated by metabolic or oxidative stress remains poorly understood. Here, we show that M- and E-BCSCs rely on distinct metabolic pathways and display markedly different sensitivities to inhibitors of glycolysis and redox metabolism. Metabolic or oxidative stress generated by 2DG, H2 O2 , or hypoxia promotes the transition of ROSlo M-BCSCs to a ROShi E-state...
July 3, 2018: Cell Metabolism
Tobias Janowitz
Tumors interact reciprocally with their hosts' physiology and metabolism, making cancer a systemic disease. In this issue of Cell Metabolism, Borniger et al. (2018) demonstrate this phenomenon by linking the endocrine control of food intake with sleep behavior and liver metabolism in a mouse model of non-metastatic breast carcinoma.
July 3, 2018: Cell Metabolism
Marcus D Goncalves, Lewis C Cantley
Glycolysis is prudently regulated and coupled to cell growth. Phosphofructokinase 2 controls glycolytic flux by generating fructose 2,6-bisphosphate, an allosteric activator of phosphofructokinase 1. In a recent paper in Nature, Dasgupta et al. address the novel role of PFKFB4, an isoform of phosphofructokinase 2, in regulating gene expression to promote tumor growth.
July 3, 2018: Cell Metabolism
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