LIVIVO - Search results -

Search results

Result 1 - 10 of total 94

Search options

Article ; Online: Comparison of Transplantation of Lung Organoid Cell Types: One Size Does Not Fit All.

Ararat, Erhan / Louie, Sharon M / Lu, Emery / Paschini, Margherita / Raiser, David M / Kim, Carla F

American journal of respiratory cell and molecular biology

2022 Volume 66, Issue 3, Page(s) 340–343

MeSH term(s)	Lung ; Organoids
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2021-0263LE
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2851: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: PR1P, a VEGF-stabilizing peptide, reduces injury and inflammation in acute lung injury and ulcerative colitis animal models.

Adini, Avner / Ko, Victoria H / Puder, Mark / Louie, Sharon M / Kim, Carla F / Baron, Joseph / Matthews, Benjamin D

Frontiers in immunology

2023 Volume 14, Page(s) 1168676

Abstract: Acute Respiratory Distress Syndrome (ARDS) and Ulcerative Colitis (UC) are each characterized by tissue damage and uncontrolled inflammation. Neutrophils and other inflammatory cells play a primary role in disease progression by acutely responding to ... ...

Abstract	Acute Respiratory Distress Syndrome (ARDS) and Ulcerative Colitis (UC) are each characterized by tissue damage and uncontrolled inflammation. Neutrophils and other inflammatory cells play a primary role in disease progression by acutely responding to direct and indirect insults to tissue injury and by promoting inflammation through secretion of inflammatory cytokines and proteases. Vascular Endothelial Growth Factor (VEGF) is a ubiquitous signaling molecule that plays a key role in maintaining and promoting cell and tissue health, and is dysregulated in both ARDS and UC. Recent evidence suggests a role for VEGF in mediating inflammation, however, the molecular mechanism by which this occurs is not well understood. We recently showed that PR1P, a 12-amino acid peptide that binds to and upregulates VEGF, stabilizes VEGF from degradation by inflammatory proteases such as elastase and plasmin thereby limiting the production of VEGF degradation products (fragmented VEGF (fVEGF)). Here we show that fVEGF is a neutrophil chemoattractant
MeSH term(s)	Animals ; Mice ; Rats ; Acute Lung Injury/metabolism ; Colitis, Ulcerative/drug therapy ; Cytokines/metabolism ; Disease Models, Animal ; Inflammation/chemically induced ; Interleukin-6 ; Peptide Hydrolases ; Peptides/adverse effects ; Respiratory Distress Syndrome/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Cytokines ; Interleukin-6 ; Peptide Hydrolases (EC 3.4.-) ; Peptides ; Vascular Endothelial Growth Factor A ; PR1P peptide
Language	English
Publishing date	2023-04-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1168676
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: FATP5 is indispensable for the growth of intrahepatic cholangiocarcinoma.

Shihadih, Diyala / Wang, Xue / Zushin, Peter-James H / Khodakivskyi, Pavlo / Park, Hyo Min / Tso, Emily / Shiblak, Jena / Misic, Angela / Louie, Sharon M / Ward, Catherine / Hellerstein, Marc / Nomura, Daniel K / Goun, Elena / Urigo, Francesco / Calvisi, Diego F / Chen, Xin / Stahl, Andreas

Molecular cancer research : MCR

2024

Abstract: Altered lipid metabolism is a common hallmark of various cancers, including Intrahepatic Cholangiocarcinoma (ICC), a highly lethal carcinoma that lacks effective treatment options. To elucidate the lipid metabolism changes in ICC, we coupled the ... ...

Abstract	Altered lipid metabolism is a common hallmark of various cancers, including Intrahepatic Cholangiocarcinoma (ICC), a highly lethal carcinoma that lacks effective treatment options. To elucidate the lipid metabolism changes in ICC, we coupled the expression of the firefly luciferase gene (FFL) to AKT1 (AKT-FFL) via an IRES linker, and then hydrodynamically injected mice with AKT-FFL and Notch1 intracellular cytoplasmic domain (NICD) to establish a luciferase-positive ICC model. This model not only enabled us to monitor and quantify tumor growth by injecting the mice with luciferin, but also allowed us to assess the fatty acid uptake rate by injecting the mice with free fatty acid luciferin (FFA-Luc). The ICC model exhibited robust uptake of exogenous fatty acids compared with the HCC model induced by AKT-FFL/ neuroblastoma Ras (Ras). Lipidomics analysis showed a dramatically higher level of fatty acid in ICC, further supporting the increased fatty acids uptake. Mechanistic studies identified FATP5 as the predominant mediator of fatty acid uptake required for ICC growth using Fatp5 knockout mice and AAV-based shRNA silencing of Fatp5. Our study discovered a novel therapeutic target for the treatment of ICC and shed light on the contributions of lipid metabolism to ICC development. Implications: This study provides the first in vivo evidence that FATP5 is a potential therapeutic target for treating ICC.
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-23-0389
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5744: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging.

Benjamin, Daniel I / Brett, Jamie O / Both, Pieter / Benjamin, Joel S / Ishak, Heather L / Kang, Jengmin / Kim, Soochi / Chung, Mingyu / Arjona, Marina / Nutter, Christopher W / Tan, Jenna H / Krishnan, Ananya K / Dulay, Hunter / Louie, Sharon M / de Morree, Antoine / Nomura, Daniel K / Rando, Thomas A

Cell metabolism

2023 Volume 35, Issue 3, Page(s) 472–486.e6

Abstract: With age, skeletal muscle stem cells (MuSCs) activate out of quiescence more slowly and with increased death, leading to defective muscle repair. To explore the molecular underpinnings of these defects, we combined multiomics, single-cell measurements, ... ...

Abstract	With age, skeletal muscle stem cells (MuSCs) activate out of quiescence more slowly and with increased death, leading to defective muscle repair. To explore the molecular underpinnings of these defects, we combined multiomics, single-cell measurements, and functional testing of MuSCs from young and old mice. The multiomics approach allowed us to assess which changes are causal, which are compensatory, and which are simply correlative. We identified glutathione (GSH) metabolism as perturbed in old MuSCs, with both causal and compensatory components. Contrary to young MuSCs, old MuSCs exhibit a population dichotomy composed of GSH
MeSH term(s)	Mice ; Animals ; Muscle, Skeletal/metabolism ; Multiomics ; Stem Cells/metabolism ; Cellular Senescence ; Aging/physiology
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2023.02.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6169: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Progenitor potential of lung epithelial organoid cells in a transplantation model.

Louie, Sharon M / Moye, Aaron L / Wong, Irene G / Lu, Emery / Shehaj, Andrea / Garcia-de-Alba, Carolina / Ararat, Erhan / Raby, Benjamin A / Lu, Bao / Paschini, Margherita / Bronson, Roderick T / Kim, Carla F

Cell reports

2022 Volume 39, Issue 2, Page(s) 110662

Abstract: Lung progenitor cells are crucial for regeneration following injury, yet it is unclear whether lung progenitor cells can be functionally engrafted after transplantation. We transplanted organoid cells derived from alveolar type II (AT2) cells enriched by ...

Abstract	Lung progenitor cells are crucial for regeneration following injury, yet it is unclear whether lung progenitor cells can be functionally engrafted after transplantation. We transplanted organoid cells derived from alveolar type II (AT2) cells enriched by SCA1-negative status (SNO) or multipotent SCA1-positive progenitor cells (SPO) into injured mouse lungs. Transplanted SNO cells are retained in the alveolar regions, whereas SPO cells incorporate into airway and alveolar regions. Single-cell transcriptomics demonstrate that transplanted SNO cells are comparable to native AT2 cells. Transplanted SPO cells exhibit transcriptional hallmarks of alveolar and airway cells, as well as transitional cell states identified in disease. Transplanted cells proliferate after re-injury of recipient mice and retain organoid-forming capacity. Thus, lung epithelial organoid cells exhibit progenitor cell functions after reintroduction to the lung. This study reveals methods to interrogate lung progenitor cell potential and model transitional cell states relevant to pathogenic features of lung disease in vivo.
MeSH term(s)	Animals ; Cell Differentiation ; Epithelial Cells ; Lung ; Mice ; Organoids ; Spinocerebellar Ataxias ; Stem Cells
Language	English
Publishing date	2022-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110662
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Fasting induces a highly resilient deep quiescent state in muscle stem cells via ketone body signaling.

Benjamin, Daniel I / Both, Pieter / Benjamin, Joel S / Nutter, Christopher W / Tan, Jenna H / Kang, Jengmin / Machado, Leo A / Klein, Julian D D / de Morree, Antoine / Kim, Soochi / Liu, Ling / Dulay, Hunter / Feraboli, Ludovica / Louie, Sharon M / Nomura, Daniel K / Rando, Thomas A

Cell metabolism

2022 Volume 34, Issue 6, Page(s) 902–918.e6

Abstract: Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here, we report that fasting slows muscle repair both immediately after the conclusion of fasting ... ...

Abstract	Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here, we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Furthermore, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a nonmetabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs, leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.
MeSH term(s)	3-Hydroxybutyric Acid ; Fasting/physiology ; Muscles ; Myoblasts ; Tumor Suppressor Protein p53
Chemical Substances	Tumor Suppressor Protein p53 ; 3-Hydroxybutyric Acid (TZP1275679)
Language	English
Publishing date	2022-05-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2022.04.012
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6169: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis.

Volkmar, Norbert / Thezenas, Maria-Laetitia / Louie, Sharon M / Juszkiewicz, Szymon / Nomura, Daniel K / Hegde, Ramanujan S / Kessler, Benedikt M / Christianson, John C

Journal of cell science

2019 Volume 132, Issue 2

Abstract: The eukaryotic endoplasmic reticulum (ER) membrane contains essential complexes that oversee protein biogenesis and lipid metabolism, impacting nearly all aspects of cell physiology. The ER membrane protein complex (EMC) is a newly described ... ...

Abstract	The eukaryotic endoplasmic reticulum (ER) membrane contains essential complexes that oversee protein biogenesis and lipid metabolism, impacting nearly all aspects of cell physiology. The ER membrane protein complex (EMC) is a newly described transmembrane domain (TMD) insertase linked with various phenotypes, but whose clients and cellular responsibilities remain incompletely understood. We report that EMC deficiency limits the cellular boundaries defining cholesterol tolerance, reflected by diminished viability with limiting or excessive extracellular cholesterol. Lipidomic and proteomic analyses revealed defective biogenesis and concomitant loss of the TMD-containing ER-resident enzymes sterol-O-acyltransferase 1 (SOAT1) and squalene synthase (SQS, also known as FDFT1), which serve strategic roles in the adaptation of cells to changes in cholesterol availability. Insertion of the weakly hydrophobic tail-anchor (TA) of SQS into the ER membrane by the EMC ensures sufficient flux through the sterol biosynthetic pathway while biogenesis of polytopic SOAT1 promoted by the EMC provides cells with the ability to store free cholesterol as inert cholesteryl esters. By facilitating insertion of TMDs that permit essential mammalian sterol-regulating enzymes to mature accurately, the EMC is an important biogenic determinant of cellular robustness to fluctuations in cholesterol availability.This article has an associated First Person interview with the first author of the paper.
MeSH term(s)	Cell Line, Tumor ; Cholesterol/biosynthesis ; Cholesterol/genetics ; Endoplasmic Reticulum/enzymology ; Endoplasmic Reticulum/genetics ; Farnesyl-Diphosphate Farnesyltransferase/genetics ; Farnesyl-Diphosphate Farnesyltransferase/metabolism ; Humans ; Intracellular Membranes/enzymology ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Sterol O-Acyltransferase/genetics ; Sterol O-Acyltransferase/metabolism
Chemical Substances	Multienzyme Complexes ; Cholesterol (97C5T2UQ7J) ; Sterol O-Acyltransferase (EC 2.3.1.26) ; sterol O-acyltransferase 1 (EC 2.3.1.26) ; Farnesyl-Diphosphate Farnesyltransferase (EC 2.5.1.21)
Language	English
Publishing date	2019-01-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.223453
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 14: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Mechanisms linking obesity and cancer.

Louie, Sharon M / Roberts, Lindsay S / Nomura, Daniel K

Biochimica et biophysica acta

2013 Volume 1831, Issue 10, Page(s) 1499–1508

Abstract: The incidence of obesity in US adults has been steadily increasing over the past few decades. Many comorbidities associated with obesity have been well-established such as type 2 diabetes and cardiovascular diseases. However, more recently an ... ...

Abstract	The incidence of obesity in US adults has been steadily increasing over the past few decades. Many comorbidities associated with obesity have been well-established such as type 2 diabetes and cardiovascular diseases. However, more recently an epidemiological relationship between obesity and the prevalence of a variety of cancers has also been uncovered. The shift of the paradigm surrounding white adipose tissue function from purely an energy storage tissue, to one that has both endocrine and metabolic relevance, has led to several mechanisms implicated in how obesity drives cancer prevalence and cancer deaths. Currently, there are four categories into which these mechanisms fall - increased lipids and lipid signaling, inflammatory responses, insulin resistance, and adipokines. In this review, we examine each of these categories and the mechanisms through which they drive cancer pathogenesis. Understanding the relationship(s) between obesity and cancer and especially the nodal points of control in these cascades will be essential in developing effective therapeutics or interventions for combating this deadly combination. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
MeSH term(s)	Adipokines/physiology ; Humans ; Inflammation/complications ; Inflammation/physiopathology ; Insulin Resistance ; Lipids/blood ; Neoplasms/complications ; Neoplasms/metabolism ; Neoplasms/physiopathology ; Obesity/complications ; Obesity/metabolism ; Obesity/physiopathology ; Signal Transduction
Chemical Substances	Adipokines ; Lipids
Language	English
Publishing date	2013-03-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbalip.2013.02.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.247: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking.

Ibars, Maria / Maier, Matthew T / Yulyaningsih, Ernie / Perez, Luz / Cheang, Rachel / Vilhelmsson, Anna / Louie, Sharon M / Wegner, Scott A / Yuan, Xiaoyi / Eltzschig, Holger K / Hopf, Frederic W / Nomura, Daniel K / Koliwad, Suneil K / Xu, Allison W

American journal of physiology. Endocrinology and metabolism

2020 Volume 318, Issue 5, Page(s) E655–E666

Abstract: Excessive alcohol consumption, including binge drinking, is a common cause of fatty liver disease. Binge drinking rapidly induces hepatic steatosis, an early step in the pathogenesis of chronic liver injury. Despite its prevalence, the process by which ... ...

Abstract	Excessive alcohol consumption, including binge drinking, is a common cause of fatty liver disease. Binge drinking rapidly induces hepatic steatosis, an early step in the pathogenesis of chronic liver injury. Despite its prevalence, the process by which excessive alcohol consumption promotes hepatic lipid accumulation remains unclear. Alcohol exerts potent effects on the brain, including hypothalamic neurons crucial for metabolic regulation. However, whether or not the brain plays a role in alcohol-induced hepatic steatosis is unknown. In the brain, alcohol increases extracellular levels of adenosine, a potent neuromodulator, and previous work implicates adenosine signaling as being important for the development of alcoholic fatty liver disease. Acute alcohol exposure also increases both the activity of agouti-related protein (AgRP)-expressing neurons and AgRP immunoreactivity. Here, we show that adenosine receptor A
MeSH term(s)	Agouti-Related Protein/metabolism ; Animals ; Binge Drinking/metabolism ; Fatty Liver, Alcoholic/metabolism ; Hypothalamus/metabolism ; Lipid Metabolism/physiology ; Liver/metabolism ; Male ; Mice ; Neurons/metabolism
Chemical Substances	Agouti-Related Protein ; Agrp protein, mouse
Language	English
Publishing date	2020-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00218.2019
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.89: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Regulation of Hepatic Lipid Accumulation and Distribution by Agouti-Related Protein in Male Mice.

Maier, Matthew T / Vilhelmsson, Anna / Louie, Sharon M / Vagena, Eirini / Nomura, Daniel K / Koliwad, Suneil K / Xu, Allison W

Endocrinology

2018 Volume 159, Issue 6, Page(s) 2408–2420

Abstract: Proper regulation of energy metabolism requires neurons in the central nervous system to respond dynamically to signals that reflect the body's energy reserve, and one such signal is leptin. Agouti-related protein (AgRP) is a hypothalamic neuropeptide ... ...

Abstract	Proper regulation of energy metabolism requires neurons in the central nervous system to respond dynamically to signals that reflect the body's energy reserve, and one such signal is leptin. Agouti-related protein (AgRP) is a hypothalamic neuropeptide that is markedly upregulated in leptin deficiency, a condition that is associated with severe obesity, diabetes, and hepatic steatosis. Because deleting AgRP in mice does not alter energy balance, we sought to determine whether AgRP plays an indispensable role in regulating energy and hepatic lipid metabolism in the sensitized background of leptin deficiency. We generated male mice that are deficient for both leptin and AgRP [double-knockout (DKO)]. DKO mice and ob/ob littermates had similar body weights, food intake, energy expenditure, and plasma insulin levels, although DKO mice surprisingly developed heightened hyperglycemia with advancing age. Overall hepatic lipid content was reduced in young prediabetic DKO mice, but not in the older diabetic counterparts. Intriguingly, however, both young and older DKO mice had an altered zonal distribution of hepatic lipids with reduced periportal lipid deposition. Moreover, leptin stimulated, whereas AgRP inhibited, hepatic sympathetic activity. Ablating sympathetic nerves to the liver, which primarily innervate the portal regions, produced periportal lipid accumulation in wild-type mice. Collectively, our results highlight AgRP as a regulator of hepatic sympathetic activity and metabolic zonation.
MeSH term(s)	Agouti-Related Protein/genetics ; Agouti-Related Protein/physiology ; Animals ; Fatty Liver/genetics ; Fatty Liver/metabolism ; Fatty Liver/pathology ; Leptin/genetics ; Lipid Metabolism/genetics ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Obese ; Obesity, Morbid/genetics ; Obesity, Morbid/metabolism ; Obesity, Morbid/pathology ; Tissue Distribution/genetics
Chemical Substances	Agouti-Related Protein ; Leptin
Language	English
Publishing date	2018-05-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2018-00040
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.72: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito