Abstract：
:In advanced atherosclerosis, macrophage apoptosis coupled with defective phagocytic clearance of the apoptotic cells (efferocytosis) promotes plaque necrosis, which precipitates acute atherothrombotic cardiovascular events. Oxidative and endoplasmic reticulum (ER) stress in macrophages are important causes of advanced lesional macrophage apoptosis. We now show that proapoptotic oxidative/ER stress inducers trigger another stress reaction in macrophages, autophagy. Inhibition of autophagy by silencing ATG5 or other autophagy mediators enhances apoptosis and NADPH oxidase-mediated oxidative stress while at the same time rendering the apoptotic cells less well recognized by efferocytes. Most importantly, macrophage ATG5 deficiency in fat-fed Ldlr(-/-) mice increases apoptosis and oxidative stress in advanced lesional macrophages, promotes plaque necrosis, and worsens lesional efferocytosis. These findings reveal a protective process in oxidatively stressed macrophages relevant to plaque necrosis, suggesting a mechanism-based strategy to therapeutically suppress atherosclerosis progression and its clinical sequelae.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Liao X,Sluimer JC,Wang Y,Subramanian M,Brown K,Pattison JS,Robbins J,Martinez J,Tabas Idoi
10.1016/j.cmet.2012.01.022subject
Has Abstractpub_date
2012-04-04 00:00:00pages
545-53issue
4eissn
1550-4131issn
1932-7420pii
S1550-4131(12)00062-9journal_volume
15pub_type
杂志文章相关文献
Cell Metabolism文献大全abstract：:Nuclear receptor signaling plays an important role in energy metabolism. In this study we demonstrate that the nuclear receptor corepressor RIP140 is a key regulator of metabolism in skeletal muscle. RIP140 is expressed in a fiber type-specific manner, and manipulation of its levels in null, heterozygous, and transgen...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2007.08.004
更新日期：2007-09-01 00:00:00
abstract：:Obesity-related morbidity and mortality are related to fat accumulation and fat distribution in humans. Two large-scale meta-analyses recently published in Nature by Shungin et al. (2015) and Locke et al. (2015) report novel genetic associations for central and overall obesity; these greatly advance our understanding ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2015.03.016
更新日期：2015-04-07 00:00:00
abstract：:Osteoclasts are the primary cells that resorb bone; they require high energy levels to degrade bone matrix, releasing minerals to maintain calcium homeostasis. Recent work on osteoclast differentiation and activity highlights an important role for mitochondrial biogenesis and explores the role of iron transferrin in g...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2009.04.005
更新日期：2009-05-01 00:00:00
abstract：:Although the concept of Syndrome X was introduced in the Banting Medal address of 1988 (Reaven, 1988), the notion that led to its genesis had started approximately 50 years earlier. In this short history, an attempt will be made to trace the two paths of scientific discovery that were formally merged in New Orleans in...
journal_title：Cell metabolism
pub_type： 历史文章,杂志文章
doi：10.1016/j.cmet.2004.12.001
更新日期：2005-01-01 00:00:00
abstract：:Cyclic AMP (cAMP) and Ca(2+) are key regulators of exocytosis in many cells, including insulin-secreting beta cells. Glucose-stimulated insulin secretion from beta cells is pulsatile and involves oscillations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), but little is known about the detailed kinetics of cAMP...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2008.06.003
更新日期：2008-07-01 00:00:00
abstract：:Myriad strategies have been explored to compensate for the lack of dystrophin or to skip mutations that cause the lethal disease Duchenne muscular dystrophy (DMD). A new study shows that gene editing strategies used by bacteria can be applied in zygotes of a mouse model of DMD to correct the genetic defect that causes...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2014.11.011
更新日期：2014-12-02 00:00:00
abstract：:The contribution of interleukin (IL)-6 signaling in obesity-induced inflammation remains controversial. To specifically define the role of hepatic IL-6 signaling in insulin action and resistance, we have generated mice with hepatocyte-specific IL-6 receptor (IL-6R) alpha deficiency (IL-6Ralpha(L-KO) mice). These anima...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2010.06.011
更新日期：2010-09-08 00:00:00
abstract：:Diurnal oscillations of gene expression controlled by the circadian clock and its connected feeding rhythm enable organisms to coordinate their physiologies with daily environmental cycles. While available techniques yielded crucial insights into regulation at the transcriptional level, much less is known about tempor...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2016.10.003
更新日期：2017-01-10 00:00:00
abstract：:Injection of the peptide hormone ghrelin stimulates food intake in mice and humans. However, mice born without ghrelin demonstrate no significant loss of appetite. This paradox suggests either that compensation develops in mice born without ghrelin or that ghrelin is not essential for appetite control. To distinguish ...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2014.04.007
更新日期：2014-07-01 00:00:00
abstract：:Current understanding of microRNA (miRNA) biology is limited, and antisense oligonucleotide (ASO) inhibition of miRNAs is a powerful technique for their functionalization. To uncover the role of the liver-specific miR-122 in the adult liver, we inhibited it in mice with a 2'-O-methoxyethyl phosphorothioate ASO. miR-12...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2006.01.005
更新日期：2006-02-01 00:00:00
abstract：:Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss rem...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2015.11.004
更新日期：2016-02-09 00:00:00
abstract：:In mammals, most metabolic processes are influenced by biological clocks and feeding rhythms. The mechanisms that couple metabolism to circadian oscillators are just emerging. NAD-dependent enzymes (e.g., Sirtuins and poly[ADP-ribose] polymerases), redox- and/or temperature-dependent transcription factors (e.g., CLOCK...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2011.01.006
更新日期：2011-02-02 00:00:00
abstract：:Intestinal microbial communities regulate a range of host physiological functions, from energy harvest and glucose homeostasis to immune development and regulation. Suez et al. (2014) recently demonstrated that artificial sweeteners alter gut microbial communities, leading to glucose intolerance in both mice and human...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2014.10.012
更新日期：2014-11-04 00:00:00
abstract：:Sphingolipids have garnered attention for their role in insulin resistance and lipotoxic cell death. We have developed transgenic mice inducibly expressing acid ceramidase that display a reduction in ceramides in adult mouse tissues. Hepatic overexpression of acid ceramidase prevents hepatic steatosis and prompts impr...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2015.06.007
更新日期：2015-08-04 00:00:00
abstract：:Evolution favored individuals with superior cognitive and physical abilities under conditions of limited food sources, and brain function can therefore be optimized by intermittent dietary energy restriction (ER) and exercise. Such energetic challenges engage adaptive cellular stress-response signaling pathways in neu...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2012.08.012
更新日期：2012-12-05 00:00:00
abstract：:Accumulating evidence suggests that changes in the metabolic signature of astrocytes underlie their response to neuroinflammation, but how proinflammatory stimuli induce these changes is poorly understood. By monitoring astrocytes following acute cortical injury, we identified a differential and region-specific remode...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2013.11.005
更新日期：2013-12-03 00:00:00
abstract：:Skin aging is of considerable interest from various perspectives, ranging from aesthetics to cancer development. Zhang et al. (2019) elucidate an immunological consequence of aging in the adipose layer of skin. Age-dependent increases in TGF-β signaling impair fibroblast adipogenic potential that results in impaired a...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2019.02.006
更新日期：2019-03-05 00:00:00
abstract：:Cancer cells frequently hijack normal metabolic pathways to promote their growth and metastasis. Two recent papers by Knott et al. (2018) and Pavlova et al. (2018) demonstrate that asparagine and glutamine work in concert to drive tumor growth and metastasis through modulation of cell survival, growth, and EMT regulat...
journal_title：Cell metabolism
pub_type： 评论
doi：10.1016/j.cmet.2018.04.012
更新日期：2018-05-01 00:00:00
abstract：:Physical performance relies on the concerted action of myriad responses, many of which are under circadian clock control. Little is known, however, regarding the time-dependent effect on exercise performance at the molecular level. We found that both mice and humans exhibit daytime variance in exercise capacity betwee...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2019.03.012
更新日期：2019-07-02 00:00:00
abstract：:Mutations resulting in reduced signaling of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis are associated with increased life- and healthspan across model organisms. Similar findings have been noted in human cohorts with functional mutations in the somatotropic axis, suggesting that this pathway may a...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2016.05.014
更新日期：2016-06-14 00:00:00
abstract：:Many of the established positive health benefits of exercise have been documented by historical discoveries in the field of exercise physiology. These investigations often assess limits: the limits of performance, or the limits of exercise-induced health benefits. Indeed, several key findings have been informed by stu...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2017.04.018
更新日期：2017-05-02 00:00:00
abstract：:Phosphorylation of glycogen has been known for decades; however, the basic metabolic pathways responsible for this modification are unknown. In this issue, Tagliabracci et al. (2011) report the enzyme responsible for incorporating phosphate and the chemical nature of the phosphate linkage, providing a framework for ex...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2011.02.006
更新日期：2011-03-02 00:00:00
abstract：:Mutations of mtDNA cause mitochondrial diseases and are implicated in age-associated diseases and aging. Pathogenic mtDNA mutations are often present in a fraction of all mtDNA copies, and it has been widely debated whether the proportion of mutant genomes or the absolute number of wild-type molecules determines if ox...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2017.07.003
更新日期：2017-08-01 00:00:00
abstract：:While mesenchymal stem cells (MSCs) are rapidly cleared from the body following systemic transplantation, their therapeutic benefits typically persist. In this issue, Liu et al. (2015) reveal that the ability of transplanted MSCs to alleviate osteoporosis in systemic lupus erythematosus is maintained through epigeneti...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2015.09.019
更新日期：2015-10-06 00:00:00
abstract：:The mechanism by which pharmacologic administration of the hormone FGF21 increases energy expenditure to cause weight loss in obese animals is unknown. Here we report that FGF21 acts centrally to exert its effects on energy expenditure and body weight in obese mice. Using tissue-specific knockout mice, we show that βK...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2014.07.012
更新日期：2014-10-07 00:00:00
abstract：:Signaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARgamma and C/EBPalpha. Here we demonstrate that the IRE1alpha-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryo...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2009.04.009
更新日期：2009-06-01 00:00:00
abstract：:Metformin is the first-line therapy for type 2 diabetes, but there are large inter-individual variations in responses to this drug. Its mechanism of action is not fully understood, but activation of AMP-activated protein kinase (AMPK) and changes in the gut microbiota appear to be important. The inhibitory role of mic...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2020.07.012
更新日期：2020-10-06 00:00:00
abstract：:Cancer stem cells (CSCs) are critical for cancer progression and chemoresistance. How lipid metabolism regulates CSCs and chemoresistance remains elusive. Here, we demonstrate that JAK/STAT3 regulates lipid metabolism, which promotes breast CSCs (BCSCs) and cancer chemoresistance. Inhibiting JAK/STAT3 blocks BCSC self...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2017.11.001
更新日期：2018-01-09 00:00:00
abstract：:Embryonic stem cells (ESCs) manifest a unique metabolism that is intimately linked to their pluripotent state. In this issue, Moussaieff et al. (2015) find that ESCs utilize glycolysis to fuel high rates of cytosolic acetyl-CoA synthesis to maintain the histone acetylation required for pluripotency. ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2015.02.011
更新日期：2015-03-03 00:00:00
abstract：:The symbiotic gut microbiota modulate health and disease of the host through a series of transgenomic metabolic and immune regulatory axes. We explore connections between microbiome composition and function related to individual metabolic phenotypes and consider these interactions as possible targets for developing ne...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2012.10.007
更新日期：2012-11-07 00:00:00
