Abstract：
:Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Loh NY,Neville MJ,Marinou K,Hardcastle SA,Fielding BA,Duncan EL,McCarthy MI,Tobias JH,Gregson CL,Karpe F,Christodoulides Cdoi
10.1016/j.cmet.2015.01.009subject
Has Abstractpub_date
2015-02-03 00:00:00pages
262-273issue
2eissn
1550-4131issn
1932-7420pii
S1550-4131(15)00010-8journal_volume
21pub_type
杂志文章相关文献
Cell Metabolism文献大全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：:We review mechanisms that regulate production of glucose by the liver, focusing on areas of budding consensus, and endeavoring to provide a candid assessment of lingering controversies. We also attempt to reconcile data from tracer studies in humans and large animals with the growing compilation of mouse knockouts tha...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2011.06.003
更新日期：2011-07-06 00:00:00
abstract：:Light is a powerful synchronizer of the circadian rhythms, and bright light therapy is known to improve metabolic and hormonal status of circadian rhythm sleep disorders, although its mechanism is poorly understood. In the present study, we revealed that light induces gene expression in the adrenal gland via the supra...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2005.09.009
更新日期：2005-11-01 00:00:00
abstract：:Nicotinamide phosphoribosyltransferase (NAMPT), the key NAD(+) biosynthetic enzyme, has two different forms, intra- and extracellular (iNAMPT and eNAMPT), in mammals. However, the significance of eNAMPT secretion remains unclear. Here we demonstrate that deacetylation of iNAMPT by the mammalian NAD(+)-dependent deacet...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2015.04.002
更新日期：2015-05-05 00:00:00
abstract：:In this issue of Cell Metabolism, Mounier et al. (2013) show that AMPKα1 is a crucial contributor to the regeneration of damaged muscle tissues, acting in macrophages at the nexus between proinflammatory debris removal and resolution of muscle tissue inflammation. ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2013.07.011
更新日期：2013-08-06 00:00:00
abstract：:Immune cell function and fate are intimately linked to engagement of metabolic pathways. The contribution of core metabolic pathways to immune cell bioenergetics has been vigorously investigated in recent years. However, precisely how other peripheral metabolic pathways support immune cells beyond energy generation is...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2017.06.019
更新日期：2017-07-05 00:00:00
abstract：:Plasticity in growth and reproductive behavior is found in many vertebrate species, but is common in male teleost fish. Typically, "bourgeois" males are considerably larger and defend breeding territories while "parasitic" variants are small and use opportunistic breeding strategies. The P locus mediates this phenotyp...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2011.12.014
更新日期：2012-02-08 00:00:00
abstract：:Oxidants are thought to damage cells, and stem cells are viewed as particularly vulnerable to oxidative stress. Now, a new study (Morimoto et al., 2013) suggests that the self-renewal of certain stem cells may actually require reactive oxygen species (ROS). ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2013.06.007
更新日期：2013-07-02 00:00:00
abstract：:The conversion of lipolysis-derived fatty acids into ketone bodies (ketogenesis) is a crucial metabolic adaptation to prolonged periods of food scarcity. The process occurs primarily in liver mitochondria and is initiated by fatty-acid-mediated stimulation of the ligand-operated transcription factor, peroxisome prolif...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2018.09.014
更新日期：2019-01-08 00:00:00
abstract：:Nutritional and pharmacological stimuli can dramatically alter the cellular phenotypes in white adipose tissue (WAT). Utilizing genetic lineage tracing techniques, we demonstrate that brown adipocytes (BA) that are induced by β3-adrenergic receptor activation in abdominal WAT arise from the proliferation and different...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2012.03.009
更新日期：2012-04-04 00:00:00
abstract：:The canonical notion that type 1 diabetes (T1D) results following a complete destruction of β cells has recently been questioned as small amounts of C-peptide are detectable in patients with long-standing disease. We analyzed protein and gene expression levels for proinsulin, insulin, C-peptide, and islet amyloid poly...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2017.08.013
更新日期：2017-09-05 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：:PTPMT1 was the first protein tyrosine phosphatase found localized to the mitochondria, but its biological function was unknown. Herein, we demonstrate that whole body deletion of Ptpmt1 in mice leads to embryonic lethality, suggesting an indispensable role for PTPMT1 during development. Ptpmt1 deficiency in mouse embr...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2011.04.007
更新日期：2011-06-08 00:00:00
abstract：:In this issue of Cell Metabolism, Macdougall et al. (2018) identify two subsets of conventional dendritic cells in visceral adipose tissue and demonstrate that these subsets engage distinct adipocyte-associated signaling pathways to drive their tolerogenic phenotypes in the lean state. ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2018.02.014
更新日期：2018-03-06 00:00:00
abstract：:Glucose and hormone responsiveness of pancreatic β cells is acquired during postnatal maturation and is critical for appropriate insulin secretion. In a recent issue of Cell Metabolism, Yoshihara et al. (2016) report that estrogen-related receptor γ (ERRγ) promotes functional maturation of both mouse neonatal β cells ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2016.04.026
更新日期：2016-05-10 00:00:00
abstract：:We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced s...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2018.04.021
更新日期：2018-07-03 00:00:00
abstract：:Signaling by the corticotropin-releasing factor receptor type 1 (CRFR1) plays an important role in mediating the autonomic response to stressful challenges. Multiple hypothalamic nuclei regulate sympathetic outflow. Although CRFR1 is highly expressed in the arcuate nucleus (Arc) of the hypothalamus, the identity of th...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2016.04.017
更新日期：2016-06-14 00:00:00
abstract：:Regulatory T cells maintain tolerance and prevent autoimmunity, but their suppressive effects can hinder immune responses against cancer. In Nature Immunology, Maj et al., 2017 report that regulatory T cells can execute these actions through the nucleoside adenosine even after cell death. ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2017.12.013
更新日期：2018-01-09 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：: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：: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：:The fat mass and obesity-associated (FTO) gene was placed center stage when common intronic variants within the gene were robustly associated with human obesity. Murine models of perturbed Fto expression have shown effects on body weight and composition. However, a clear understanding of the link between FTO intronic ...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2014.09.010
更新日期：2014-11-04 00:00:00
abstract：:Reverse cholesterol transport (RCT) is an antiatherogenic process in which excessive cholesterol from peripheral tissues is transported to the liver and finally excreted from the body via the bile. The nuclear receptor liver receptor homolog 1 (LRH-1) drives expression of genes regulating RCT, and its activity can be ...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2014.07.023
更新日期：2014-10-07 00:00:00
abstract：:It is still unclear if the ability of key regulators of actin cytoskeletal remodeling to influence lipid metabolism contributes to kidney injury. In this issue of Cell Metabolism, Fu et al. (2020) show that junctional adhesion molecule-like (JAML) is a novel mediator of glomerular disease progression while suggesting ...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2020.11.002
更新日期：2020-12-01 00:00:00
abstract：:Fat and muscle lipolysis involves functional interactions of adipose triglyceride lipase (ATGL), α-β hydrolase domain-containing protein 5 (ABHD5), and tissue-specific perilipins 1 and 5 (PLIN1 and PLIN5). ABHD5 potently activates ATGL, but this lipase-promoting activity is suppressed when ABHD5 is bound to PLIN prote...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2015.08.023
更新日期：2015-11-03 00:00:00
abstract：:Bile acid metabolism is tightly controlled due to the toxic effects of bile acid overload. In this issue, research from the Feng lab reports Shp2 as a novel integrator of hepatic bile acid and FGF15/FGF19 signaling, adding another layer of complexity to the control of bile acid biosynthesis. ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2014.07.019
更新日期：2014-08-05 00:00:00
abstract：:With the identification of its receptor in a highly specific region of the brain, interesting issues come to light regarding the normal physiological functions of GDF15, a secreted protein long identified as a biomarker of diverse disease states. ...
journal_title：Cell metabolism
pub_type： 评论,杂志文章
doi：10.1016/j.cmet.2017.10.017
更新日期：2017-12-05 00:00:00
abstract：: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-), origi...
journal_title：Cell metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.cmet.2018.06.007
更新日期：2018-07-03 00:00:00
abstract：:Leptin secreted by adipocytes acts on the brain to reduce food intake by regulating neuronal activity in the mediobasal hypothalamus (MBH). Obesity is associated with resistance to high circulating leptin levels. Here, we demonstrate that peripherally administered leptin activates its receptor (LepR) in median eminenc...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2013.12.015
更新日期：2014-02-04 00:00:00
abstract：:The "Rosies" of Cell Metabolism are back for the third part of the "Women in Metabolism" 2015 series. We are closing our anniversary celebrations with 14 inspiring and engaging new stories from women scientists in the metabolism field. A round of applause to all who contributed and supported this project! ...
journal_title：Cell metabolism
pub_type： 杂志文章
doi：10.1016/j.cmet.2015.11.005
更新日期：2015-12-01 00:00:00
