scholarly journals Nuclear Orphan Receptor TAK1/TR4-Deficient Mice Are Protected Against Obesity-Linked Inflammation, Hepatic Steatosis, and Insulin Resistance

Diabetes ◽  
2010 ◽  
Vol 60 (1) ◽  
pp. 177-188 ◽  
Author(s):  
Hong Soon Kang ◽  
Kyoko Okamoto ◽  
Yong-Sik Kim ◽  
Yukimasa Takeda ◽  
Carl D. Bortner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Orphan Receptor ◽  
Nuclear Orphan Receptor ◽  
Deficient Mice

scholarly journals Nuclear orphan receptor NR2F6 as a safeguard against experimental murine colitis

Gut ◽  
2017 ◽  
Vol 67 (8) ◽  
pp. 1434-1444 ◽  
Author(s):  
Victoria Klepsch ◽  
Romana R Gerner ◽  
Sebastian Klepsch ◽  
William J Olson ◽  
Herbert Tilg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Intestinal Permeability ◽  
Immune Cell ◽  
Orphan Receptor ◽  
Cell Transfer ◽  
Nuclear Orphan Receptor ◽  
T Cell Transfer ◽  
Deficient Mice

ObjectiveNuclear receptors are known to regulate both immune and barrier functions in the GI tract. The nuclear orphan receptor NR2F6 has been shown to suppress the expression of proinflammatory cytokines in T lymphocytes. NR2F6 gene expression is reduced in patients with IBS or UC, but its functional role and tissue dependency in healthy and inflamed gut have not yet been investigated.DesignIntestinal inflammation was induced in wild-type, Nr2f6-deficient, Rag1-deficient or bone marrow-reconstituted mice by administration of chemical (dextran sodium sulfate (DSS)) and immunogenic (T cell transfer) triggers. Disease phenotypes were investigated by survival, body weight, colon length and analysis of immune cell infiltrates. Additionally, histology, intestinal permeability, tight junction proteins, bacterial fluorescence in situ hybridisation, apoptosis, cell proliferation and mucus production were investigated.ResultsNr2f6-deficient mice were highly susceptible to DSS-induced colitis characterised by enhanced weight loss, increased colonic tissue destruction and immune cell infiltration together with enhanced intestinal permeability and reduced Muc2 expression. T cell transfer colitis and bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the expression of Nr2f6 in the immune compartment but on the protective role of NR2F6 in the intestinal epithelium. Mechanistically, we show that NR2F6 binds to a consensus sequence at −2 kb of the Muc2 promoter and transactivates Muc2 expression. Loss of NR2F6 alters intestinal permeability and results in spontaneous late-onset colitis in Nr2f6-deficient mice.ConclusionWe have for the first time identified a fundamental and non-redundant role of NR2F6 in protecting gut barrier homeostasis.

scholarly journals The Nuclear Orphan Receptor NR2F6 Promotes Hepatic Steatosis through Upregulation of Fatty Acid Transporter CD36

2020 ◽  
Vol 7 (21) ◽  
pp. 2002273
Author(s):  
Bing Zhou ◽  
Lijing Jia ◽  
Zhijian Zhang ◽  
Liping Xiang ◽  
Youwen Yuan ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Orphan Receptor ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Nuclear Orphan Receptor

scholarly journals Transcriptional profiling reveals a role for RORα in regulating gene expression in obesity-associated inflammation and hepatic steatosis

2011 ◽  
Vol 43 (13) ◽  
pp. 818-828 ◽  
Author(s):  
Hong Soon Kang ◽  
Kyoko Okamoto ◽  
Yukimasa Takeda ◽  
Ju Youn Beak ◽  
Kevin Gerrish ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Metabolic Diseases ◽  
Transcriptional Profiling ◽  
Critical Role ◽  
Orphan Receptor ◽  
Signaling Proteins ◽  
Expression Of Genes ◽  
And Storage

Retinoid-related orphan receptor (ROR)α4 is the major RORα isoform expressed in adipose tissues and liver. In this study we demonstrate that RORα-deficient staggerer mice (RORαsg/sg) fed with a high-fat diet (HFD) exhibited reduced adiposity and hepatic triglyceride levels compared with wild-type (WT) littermates and were resistant to the development of hepatic steatosis, adipose-associated inflammation, and insulin resistance. Gene expression profiling showed that many genes involved in triglyceride synthesis and storage, including Cidec, Cidea, and Mogat1, were expressed at much lower levels in liver of RORαsg/sg mice. In contrast, overexpression of RORα in mouse hepatoma Hepa1–6 cells significantly increased the expression of genes that were repressed in RORαsg/sg liver, including Sult1b1, Adfp, Cidea, and ApoA4. ChIP and promoter analysis suggested that several of these genes were regulated directly by RORα. In addition to reduced lipid accumulation, inflammation was greatly diminished in white adipose tissue (WAT) of RORαsg/sg mice fed with an HFD. The infiltration of macrophages and the expression of many immune response and proinflammatory genes, including those encoding various chemo/cytokines, Toll-like receptors, and TNF signaling proteins, were significantly reduced in RORαsg/sg WAT. Moreover, RORαsg/sg mice fed with an HFD were protected from the development of insulin resistance. RORαsg/sg mice consumed more oxygen and produced more carbon dioxide, suggesting increased energy expenditure in this genotype. Our study indicates that RORα plays a critical role in the regulation of several aspects of metabolic syndrome. Therefore, RORα may provide a novel therapeutic target in the management of obesity and associated metabolic diseases.

scholarly journals Enhanced Nrf2 Activity Worsens Insulin Resistance, Impairs Lipid Accumulation in Adipose Tissue, and Increases Hepatic Steatosis in Leptin-Deficient Mice

Diabetes ◽  
2012 ◽  
Vol 61 (12) ◽  
pp. 3208-3218 ◽  
Author(s):  
J. Xu ◽  
S. R. Kulkarni ◽  
A. C. Donepudi ◽  
V. R. More ◽  
A. L. Slitt
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Deficient Mice

Reduced bone formation and increased adiposity with insulin resistance in interleukin-11 deficient mice

2014 ◽  
Author(s):  
Bingzi Dong ◽  
Takeshi Kondo ◽  
Yukiyo Ohnishi ◽  
Itsuro Endo ◽  
Masahiro Abe ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Formation ◽  
Interleukin 11 ◽  
Deficient Mice

scholarly journals INSIGHTS INTO THE ROLE OF MORUS ALBA IN REVERSING OBESITY-ASSOCIATED HEPATIC STEATOSIS AND RELATED METABOLIC DISORDER IN RATS

2016 ◽  
pp. 231
Author(s):  
Hanaa H. Ahmed ◽  
Fatehya M Metwally ◽  
Hend Rashad ◽  
Asmaa M Zaazaa
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Metabolic Disorder ◽  
Ethanolic Extract ◽  
Treated Group ◽  
Morus Alba ◽  
The Other ◽  
Obese Group ◽  
Control Group

<p>ABSTRACT<br />Objective: The goal of the present study was to examine the viability of Morus alba (M. alba) ethanolic extract in repression of obesity-associated<br />hepatic steatosis and related metabolic disorder; dyslipidemia, hyperinsulinemia, and glycemic status.<br />Methods: Adult female albino rats were randomly assigned into four groups, eight rats each as follows: Group (1) control group received standard<br />rodent diet for 24 weeks. The other three groups administered high cholesterol diet for 12 weeks and served as obese group, M. alba-treated group,<br />and simvastatin-treated group.<br />Results: The current results showed an increment in thoracic circumference (TCX) and abdominal circumferences (AC) as well as body mass index<br />(BMI) in obese group. In addition, dyslipidemia, hyperinsulinemia, hyperglycemia, and insulin resistance have been elucidated in obese group.<br />Moreover, hepatic malondialdehyde (MDA), nitric oxide (NO), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin<br />values were significantly increased in obese groups versus control group. On the other hand, administration of ethanolic extract of Morus alba or<br />simvastatin could significantly lessen BMI and in addition to improve dyslipidemia in obese group. Glucose, insulin levels, and insulin resistance value<br />in serum samples demonstrated a significant reduction in obese group upon treatment with M. alba ethanolic extract or simvastatin. Furthermore,<br />noticeable depletion in hepatic MDA, NO contents, serum ALT, AST activities, and serum bilirubin level was recorded as a result of treatment with<br />either ethanolic extract of M. alba or simvastatin. Histopathological examination of liver tissue showed ballooning degeneration in the hepatocytes<br />(hepatic steatosis) associated with inflammatory cells penetration in portal zone in obese group. Meanwhile, the treatment of obese groups with<br />ethanolic extract of M. alba or simvastatin was found to restore the structural organization of the liver.<br />Conclusion: The present findings provide a novel aspect for understanding of the role of M. alba against obesity-associated liver diseases and related<br />metabolic disorder. The mechanisms underlying these effects seem to depend on the hypolipidemic potential, anti-inflammatory property, and<br />antioxidant activity of its phytochemicals.<br />Keywords: Obesity, Morus alba, Dyslipidemia, Hyperinsulinemia, Hyperglycemia, Hepatic steatosis.</p>

scholarly journals Chlorogenic Acid Improves High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice

2014 ◽  
Vol 32 (4) ◽  
pp. 1200-1209 ◽  
Author(s):  
Yongjie Ma ◽  
Mingming Gao ◽  
Dexi Liu
Keyword(s):  
Insulin Resistance ◽  
Chlorogenic Acid ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
High Fat

scholarly journals Ethnic differences in hepatic steatosis: An insulin resistance paradox?

Hepatology ◽  
2008 ◽  
Vol 49 (3) ◽  
pp. 791-801 ◽  
Author(s):  
Richard Guerrero ◽  
Gloria L. Vega ◽  
Scott M. Grundy ◽  
Jeffrey D. Browning
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Ethnic Differences

scholarly journals Inactivation of the Nuclear Orphan Receptor COUP-TFII by Small Chemicals

2017 ◽  
Vol 12 (3) ◽  
pp. 654-663 ◽  
Author(s):  
Rémy Le Guével ◽  
Frédérik Oger ◽  
Celia P. Martinez-Jimenez ◽  
Maud Bizot ◽  
Céline Gheeraert ◽  
...  
Keyword(s):  
Orphan Receptor ◽  
Nuclear Orphan Receptor
Sign in / Sign up

Export Citation Format

Share Document