Abstract：
:Small-molecule ligands of nuclear hormone receptors (NHRs) govern the transcriptional regulation of metazoan development, cell differentiation, and metabolism. However, the physiological ligands of many NHRs remain poorly characterized, primarily due to lack of robust analytical techniques. Using comparative metabolomics, we identified endogenous steroids that act as ligands of the C. elegans NHR, DAF-12, a vitamin D and liver X receptor homolog regulating larval development, fat metabolism, and lifespan. The identified molecules feature unexpected chemical modifications and include only one of two DAF-12 ligands reported earlier, necessitating a revision of previously proposed ligand biosynthetic pathways. We further show that ligand profiles are regulated by a complex enzymatic network, including the Rieske oxygenase DAF-36, the short-chain dehydrogenase DHS-16, and the hydroxysteroid dehydrogenase HSD-1. Our results demonstrate the advantages of comparative metabolomics over traditional candidate-based approaches and provide a blueprint for the identification of ligands for other C. elegans and mammalian NHRs.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Mahanti P,Bose N,Bethke A,Judkins JC,Wollam J,Dumas KJ,Zimmerman AM,Campbell SL,Hu PJ,Antebi A,Schroeder FCdoi
10.1016/j.cmet.2013.11.024subject
Has Abstractpub_date
2014-01-07 00:00:00pages
73-83issue
1eissn
1550-4131issn
1932-7420pii
S1550-4131(13)00499-3journal_volume
19pub_type
杂志文章相关文献
Cell Metabolism文献大全abstract：:High-fat diets cause peripheral leptin resistance, and dietary lipid composition affects sensitivity to leptin. We examined the role of n-3 polyunsaturated fatty acid (PUFA) in peripheral leptin resistance. Dietary PUFAs (0.4% wt/wt) caused insensitivity to peripherally but not intracerebroventricularly administered l...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2005.04.004
更新日期：2005-05-01 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：:Resveratrol induces mitochondrial biogenesis and protects against metabolic decline, but whether SIRT1 mediates these benefits is the subject of debate. To circumvent the developmental defects of germline SIRT1 knockouts, we have developed an inducible system that permits whole-body deletion of SIRT1 in adult mice. Mi...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2012.04.003
更新日期：2012-05-02 00:00:00
abstract：:The essential role of the brain in maintaining energy homeostasis has motivated the drive to define the neural circuitry that integrates external and internal stimuli to enact appropriate and consequential metabolic and behavioral responses. The hypothalamus has received significant attention in this regard given its ...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2015.09.026
更新日期：2015-12-01 00:00:00
abstract：:The importance of neuropeptides in the hypothalamus has been experimentally established. Due to difficulties in assessing function in vivo, the roles of the fast-acting neurotransmitters glutamate and GABA are largely unknown. Synaptic vesicular transporters (VGLUTs for glutamate and VGAT for GABA) are required for ve...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2007.04.001
更新日期：2007-05-01 00:00:00
abstract：:Faced with changing food availability, organisms adapt metabolism to survive. In a recent issue of Cell, Lin et al. (2009) described the acetylation of an extranuclear enzyme being regulated by acetyl-CoA. This finding connects nutrient availability, energy status, and survival. ...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2009.03.009
更新日期：2009-04-01 00:00:00
abstract：:Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a pl...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2020.02.013
更新日期：2020-04-07 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：:The basis for region-specific neuronal toxicity in Huntington disease is unknown. Here, we show that region-specific neuronal vulnerability is a substrate-driven response in astrocytes. Glucose is low in HdhQ(150/150) animals, and astrocytes in each brain region adapt by metabolically reprogramming their mitochondria ...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2019.03.004
更新日期：2019-06-04 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：:Reducing obesity requires an elevation of energy expenditure and/or a suppression of food intake. Here we show that enhancing hepatic glycolysis reduces body weight and adiposity in obese mice. Overexpression of glucokinase or 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is used to increase hepatic glycolysis....
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2005.07.003
更新日期：2005-08-01 00:00:00
abstract：:During conditions of impaired bile flow (cholestasis), increased serum bile acids (BAs) are prognostic markers of sepsis. In this issue, Hao et al. (2017) show that the BA receptor FXR binds NLRP3 inflammasome in macrophages and inhibits activation of inflammasome components, thus reducing endotoxemia in cholestasis. ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2017.03.014
更新日期：2017-04-04 00:00:00
abstract：:Current evidence suggests that hypothalamic fatty acid metabolism may play a role in regulating food intake; however, confirmation that it is a physiologically relevant regulatory system of feeding is still incomplete. Here, we use pharmacological and genetic approaches to demonstrate that the physiological orexigenic...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2008.03.006
更新日期：2008-05-01 00:00:00
abstract：:Iron-dependent degradation of iron-regulatory protein 2 (IRP2) is a key event for maintenance of an appropriate intracellular concentration of iron. Although FBXL5 (F box and leucine-rich repeat protein 5) is thought to mediate this degradation, the role of FBXL5 in the control of iron homeostasis in vivo has been poo...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2011.07.011
更新日期：2011-09-07 00:00:00
abstract：:Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent profibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an e...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2013.06.016
更新日期：2013-10-01 00:00:00
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...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2012.01.022
更新日期：2012-04-04 00:00:00
abstract：:Obesity and atherosclerosis-related diseases account for over one-third of deaths in the western world. Controlling these conditions remains a major challenge due to an incomplete understanding of the molecular pathways involved. Here, we show that Wip1 phosphatase, a known negative regulator of Atm-dependent signalin...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2012.06.003
更新日期：2012-07-03 00:00:00
abstract：:The final steps in the production of adenosine triphosphate (ATP) in mitochondria are executed by a series of multisubunit complexes and electron carriers, which together constitute the oxidative phosphorylation (OXPHOS) system. OXPHOS is under dual genetic control, with communication between the nuclear and mitochond...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2005.12.001
更新日期：2006-01-01 00:00:00
abstract：:Despite the prevalence of obesity and its related diseases, the signaling pathways for appetite control and satiety are not clearly understood. Here we report C. elegans quiescence behavior, a cessation of food intake and movement that is possibly a result of satiety. C. elegans quiescence shares several characteristi...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2008.01.005
更新日期：2008-03-01 00:00:00
abstract：:Animal studies have revealed brain regions that control homeostatic feeding, but the rampant overeating contributing to the obesity epidemic suggests the participation of "nonhomeostatic" control centers. Recent papers by Batterham et al. (2007) and Farooqi et al. (2007) link peptide YY(3-36) and leptin to the activat...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2007.11.007
更新日期：2007-12-01 00:00:00
abstract：:Most animal models of obesity and hyperinsulinemia are associated with increased vagal cholinergic activity. The M3 muscarinic acetylcholine receptor subtype is widely expressed in the brain and peripheral tissues and plays a key role in mediating the physiological effects of vagal activation. Here, we tested the hypo...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2006.09.008
更新日期：2006-11-01 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：:Nuclear receptors (NRs) are key regulators of gene expression and physiology. Nearly half of all human NRs lack endogenous ligands including estrogen-related receptor α (ERRα). ERRα has important roles in cancer, metabolism, and skeletal homeostasis. Affinity chromatography of tissue lipidomes with the ERRα ligand-bin...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2015.12.010
更新日期：2016-03-08 00:00:00
abstract：:Glucagon drives hepatic gluconeogenesis and maintains blood glucose levels during fasting. The mechanism that attenuates glucagon action following refeeding is not understood. The present study demonstrates an increase in perivenous liver hypoxia immediately after feeding, which stabilizes hypoxia-inducible factor 2α ...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2016.01.004
更新日期：2016-03-08 00:00:00
abstract：: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...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2017.02.012
更新日期：2017-03-07 00:00:00
abstract：:Circadian clocks, which underlie the daily rhythms in virtually all organisms, are entrained by diurnal changes in light, temperature, nutrients, and even sound. Simoni et al. (2014) demonstrate that diurnal variation in mechanical vibrations can reset circadian clock phase, providing a potential mechanism for integra...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2014.04.011
更新日期：2014-05-06 00:00:00
abstract：:While adipogenesis is known to be controlled by a complex network of transcription factors, less is known about the transcriptional cascade that initiates this process. We report here the characterization of Krüppel-like factor 4 (KLF4) as an essential early regulator of adipogenesis. Klf4 is expressed in 3T3-L1 cells...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2008.02.001
更新日期：2008-04-01 00:00:00
abstract：:In the past 3 years, we have seen a flurry of publications on single-cell RNA sequencing (RNA-seq) analyses of pancreatic islets from mouse and human. This technology holds the promise to refine cell-type signatures and discover cellular heterogeneity among the canonical endocrine cell types such as the glucagon-produ...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2018.11.016
更新日期：2019-03-05 00:00:00
abstract：:Systemic bile acid (BA) homeostasis is a critical determinant of dietary fat digestion, enterohepatic function, and postprandial thermogenesis. However, major checkpoints for the dynamics and the molecular regulation of BA homeostasis remain unknown. Here we show that hypothalamic-pituitary-adrenal (HPA) axis impairme...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2011.04.010
更新日期：2011-07-06 00:00:00
abstract：:Aerobic glycolysis (the Warburg effect) is a core hallmark of cancer, but the molecular mechanisms underlying it remain unclear. Here, we identify an unexpected central role for mTORC2 in cancer metabolic reprogramming where it controls glycolytic metabolism by ultimately regulating the cellular level of c-Myc. We sho...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2013.09.013
更新日期：2013-11-05 00:00:00
