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Cell Metabolism

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https://www.readbyqxmd.com/read/28286049/insulin-signaling-regulates-the-foxm1-plk1-cenp-a-pathway-to-promote-adaptive-pancreatic-%C3%AE-%C3%A2-cell-proliferation
#1
Jun Shirakawa, Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin R Okawa, Wei Zhang, Peng Yi, Alessandro Doria, Rohit N Kulkarni
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival...
February 26, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273483/ceramide-is-metabolized-to-acylceramide-and-stored-in-lipid-droplets
#2
Can E Senkal, Mohamed F Salama, Ashley J Snider, Janet J Allopenna, Nadia A Rana, Antonius Koller, Yusuf A Hannun, Lina M Obeid
In an approach aimed at defining interacting partners of ceramide synthases (CerSs), we found that fatty acyl-CoA synthase ACSL5 interacts with all CerSs. We demonstrate that ACSL5-generated FA-CoA was utilized with de novo ceramide for the generation of acylceramides, poorly studied ceramide metabolites. Functionally, inhibition of ceramide channeling to acylceramide enhanced accumulation of de novo ceramide and resulted in augmentation of ceramide-mediated apoptosis. Mechanistically, we show that acylceramide generation is catalyzed by diacylglycerol acyltransferase 2 (DGAT2) on lipid droplets...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273482/orai1-mediated-antimicrobial-secretion-from-pancreatic-acini-shapes-the-gut-microbiome-and-regulates-gut-innate-immunity
#3
Malini Ahuja, Daniella M Schwartz, Mayank Tandon, Aran Son, Mei Zeng, William Swaim, Michael Eckhaus, Victoria Hoffman, Yiyuan Cui, Bo Xiao, Paul F Worley, Shmuel Muallem
The gut microbiome participates in numerous physiologic functions and communicates intimately with the host immune system. Antimicrobial peptides are critical components of intestinal innate immunity. We report a prominent role for antimicrobials secreted by pancreatic acini in shaping the gut microbiome that is essential for intestinal innate immunity, barrier function, and survival. Deletion of the Ca(2+) channel Orai1 in pancreatic acini of adult mice resulted in 60%-70% mortality within 3 weeks. Despite robust activation of the intestinal innate immune response, mice lacking acinar Orai1 exhibited intestinal bacterial outgrowth and dysbiosis, ultimately causing systemic translocation, inflammation, and death...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273481/matching-dietary-amino-acid-balance-to-the-in-silico-translated-exome-optimizes-growth-and-reproduction-without-cost-to-lifespan
#4
Matthew D W Piper, George A Soultoukis, Eric Blanc, Andrea Mesaros, Samantha L Herbert, Paula Juricic, Xiaoli He, Ilian Atanassov, Hanna Salmonowicz, Mingyao Yang, Stephen J Simpson, Carlos Ribeiro, Linda Partridge
Balancing the quantity and quality of dietary protein relative to other nutrients is a key determinant of evolutionary fitness. A theoretical framework for defining a balanced diet would both reduce the enormous workload to optimize diets empirically and represent a breakthrough toward tailoring diets to the needs of consumers. Here, we report a simple and powerful in silico technique that uses the genome information of an organism to define its dietary amino acid requirements. We show for the fruit fly Drosophila melanogaster that such "exome-matched" diets are more satiating, enhance growth, and increase reproduction relative to non-matched diets...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273480/enhanced-protein-translation-underlies-improved-metabolic-and-physical-adaptations-to-different-exercise-training-modes-in-young-and-old-humans
#5
Matthew M Robinson, Surendra Dasari, Adam R Konopka, Matthew L Johnson, S Manjunatha, Raul Ruiz Esponda, Rickey E Carter, Ian R Lanza, K Sreekumaran Nair
The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273479/systems-biology-of-metabolism-a-driver-for-developing-personalized-and-precision-medicine
#6
REVIEW
Jens Nielsen
Systems biology uses mathematical models to analyze large datasets and simulate system behavior. It enables integrative analysis of different types of data and can thereby provide new insight into complex biological systems. Here will be discussed the challenges of using systems medicine for advancing the development of personalized and precision medicine to treat metabolic diseases like insulin resistance, obesity, NAFLD, NASH, and cancer. It will be illustrated how the concept of genome-scale metabolic models can be used for integrative analysis of big data with the objective of identifying novel biomarkers that are foundational for personalized and precision medicine...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273478/epigenetic-mechanisms-of-transmission-of-metabolic-disease-across-generations
#7
REVIEW
Vicencia Micheline Sales, Anne C Ferguson-Smith, Mary-Elizabeth Patti
Both human and animal studies indicate that environmental exposures experienced during early life can robustly influence risk for adult disease. Moreover, environmental exposures experienced by parents during either intrauterine or postnatal life can also influence the health of their offspring, thus initiating a cycle of disease risk across generations. In this Perspective, we focus on epigenetic mechanisms in germ cells, including DNA methylation, histone modification, and non-coding RNAs, which collectively may provide a non-genetic molecular legacy of prior environmental exposures and influence transcriptional regulation, developmental trajectories, and adult disease risk in offspring...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273477/metabolic-inputs-into-the-epigenome
#8
REVIEW
Upasna Sharma, Oliver J Rando
A number of molecular pathways play key roles in transmitting information in addition to the genomic sequence-epigenetic information-from one generation to the next. However, so-called epigenetic marks also impact an enormous variety of physiological processes, even under circumstances that do not result in heritable consequences. Perhaps inevitably, the epigenetic regulatory machinery is highly responsive to metabolic cues, as, for example, central metabolites are the substrates for the enzymes that catalyze the deposition of covalent modifications on histones, DNA, and RNA...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273476/predicting-polygenic-obesity-using-genetic-information
#9
REVIEW
Ruth J F Loos, A Cecile J W Janssens
Except in rare cases, obesity tends to be a consequence of both an unhealthy lifestyle and a genetic susceptibility to gain weight. With more than 200 common genetic variants identified, there is a growing interest in developing personalized preventive and treatment strategies to predict an individual's obesity risk. We review the literature on the prediction of obesity and show that models based on the established genetic variants have poorer predictive ability than traditional predictors, such as family history of obesity and childhood obesity...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273475/integrative-physiology-at-the-crossroads-of-nutrition-microbiota-animal-physiology-and-human-health
#10
REVIEW
François Leulier, Lesley T MacNeil, Won-Jae Lee, John F Rawls, Patrice D Cani, Martin Schwarzer, Liping Zhao, Stephen J Simpson
Nutrition is paramount in shaping all aspects of animal biology. In addition, the influence of the intestinal microbiota on physiology is now widely recognized. Given that diet also shapes the intestinal microbiota, this raises the question of how the nutritional environment and microbial assemblages together influence animal physiology. This research field constitutes a new frontier in the field of organismal biology that needs to be addressed. Here we review recent studies using animal models and humans and propose an integrative framework within which to define the study of the diet-physiology-microbiota systems and ultimately link it to human health...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273474/the-role-of-the-immune-system-in-metabolic-health-and-disease
#11
REVIEW
Niv Zmora, Stavros Bashiardes, Maayan Levy, Eran Elinav
In addition to the immune system's traditional roles of conferring anti-infectious and anti-neoplastic protection, it has been recently implicated in the regulation of systemic metabolic homeostasis. This cross-talk between the immune and the metabolic systems is pivotal in promoting "metabolic health" throughout the life of an organism and plays fundamental roles in its adaptation to ever-changing environmental makeups and nutritional availability. Perturbations in this intricate immune-metabolic cross-talk contribute to the tendency to develop altered metabolic states that may culminate in metabolic disorders such as malnutrition, obesity, type 2 diabetes mellitus (T2DM), and other features of the metabolic syndrome...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273473/lip-sync-gamma-rhythms-orchestrate-top-down-control-of-feeding-circuits
#12
Nandakumar S Narayanan, Ralph J DiLeone
Feeding involves the coordinated action of networks across many brain regions. New work recently published in Nature indicates that the prefrontal cortex, septum, and lateral hypothalamus circuits synchronize at gamma rhythms (30-90 Hz) to regulate feeding-related behaviors (Carus-Cadavieco et al., 2017).
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273472/beyond-digestion-the-pancreas-shapes-intestinal-microbiota-and-immunity
#13
Herbert Tilg, Timon E Adolph
Our understanding of the regulatory mechanisms that shape the gut microbiota is rapidly emerging. The intestinal microbial landscape is modulated by a plethora of host-extrinsic and host-intrinsic factors. In this issue of Cell Metabolism, Ahuja and colleagues (2017) demonstrate that mediators secreted by pancreatic acini shape the intestinal microbiota and intestinal immunity.
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273471/forecasting-fat-fibrosis
#14
Brett Shook, Matthew S Rodeheffer
Excess ECM and fibrosis of white adipose tissue (WAT) is associated with tissue dysfunction and type 2 diabetes. In this issue of Cell Metabolism, Marcelin et al. (2017) elucidate a key mechanism behind WAT fibrosis in which the activation of PDGFRα on adipocyte precursors drives this population toward a fibrotic phenotype.
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273470/dietary-fat-inflames-cd4-t-cell-memory-in-obesity
#15
Nicole M Chapman, Hongbo Chi
T cells promote inflammation in obesity, but how metabolic stress associated with obesity alters T cell responses remains unclear. In this issue of Cell Metabolism,Mauro et al. (2017) demonstrate that saturated fatty acids directly increase effector-memory T cell formation by amplifying T cell antigen-receptor-induced PI3K/Akt signaling.
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273469/should-i-stay-or-should-i-go-a-clash-of-%C3%AE-cell-identity
#16
Maria S Remedi
Understanding mechanisms for maintaining pancreatic islet cell fate and function is important for addressing the urgent challenge of restoring islet β- and α-cell function in T1DM. In this issue of Cell Metabolism, Chakravarthy et al. (2017) identify a genetic mechanism by which mouse β-cells are spontaneously regenerated from adult α-cells.
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273468/feeding-the-genome-in-silico-optimization-of-dietary-amino-acid-composition
#17
Michael R MacArthur, James R Mitchell
Optimizing dietary amino acid ratios to achieve maximal growth and reproduction has historically required tedious empirical studies. In this issue, Piper et al. (2017) present an in silico method of essential amino acid optimization based on the translated portion of an organism's genome, or exome.
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273467/sucralose-suppresses-food-intake
#18
LETTER
Jin Hong Park, Gil B Carvalho, Keith R Murphy, Margaux R Ehrlich, William W Ja
No abstract text is available yet for this article.
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273466/precision-metabolism-hitting-the-mark
#19
EDITORIAL
Rosalind Mott, Anne Granger, Taneli Helenius, Nikla Emambokus
No abstract text is available yet for this article.
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28215845/converting-adult-pancreatic-islet-%C3%AE-cells-into-%C3%AE-cells-by-targeting-both-dnmt1-and-arx
#20
Harini Chakravarthy, Xueying Gu, Martin Enge, Xiaoqing Dai, Yong Wang, Nicolas Damond, Carolina Downie, Kathy Liu, Jing Wang, Yuan Xing, Simona Chera, Fabrizio Thorel, Stephen Quake, Jose Oberholzer, Patrick E MacDonald, Pedro L Herrera, Seung K Kim
Insulin-producing pancreatic β cells in mice can slowly regenerate from glucagon-producing α cells in settings like β cell loss, but the basis of this conversion is unknown. Moreover, it remains unclear if this intra-islet cell conversion is relevant to diseases like type 1 diabetes (T1D). We show that the α cell regulators Aristaless-related homeobox (Arx) and DNA methyltransferase 1 (Dnmt1) maintain α cell identity in mice. Within 3 months of Dnmt1 and Arx loss, lineage tracing and single-cell RNA sequencing revealed extensive α cell conversion into progeny resembling native β cells...
March 7, 2017: Cell Metabolism
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