scholarly journals Osthole improves glucose and lipid metabolism via modulation of PPARα/γ-mediated target gene expression in liver, adipose tissue, and skeletal muscle in fatty liver rats

2015 ◽  
Vol 54 (5) ◽  
pp. 882-888 ◽  
Author(s):  
Zhi-Gang Qi ◽  
Xi Zhao ◽  
Wen Zhong ◽  
Mei-Lin Xie
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Fatty Liver ◽  
Target Gene ◽  
Target Gene Expression ◽  
Glucose And Lipid Metabolism

scholarly journals Homozygous nonsense variant in LRIF1 associated with facioscapulohumeral muscular dystrophy

Neurology ◽  
2020 ◽  
Vol 94 (23) ◽  
pp. e2441-e2447 ◽  
Author(s):  
Kohei Hamanaka ◽  
Darina Šikrová ◽  
Satomi Mitsuhashi ◽  
Hiroki Masuda ◽  
Yukari Sekiguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Target Gene ◽  
Disease Gene ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Target Gene Expression ◽  
D4z4 Repeat ◽  
Biopsy Examination ◽  
Chromatin Relaxation

ObjectiveFacioscapulohumeral muscular dystrophy (FSHD) is a heterogenetic disorder predominantly characterized by progressive facial and scapular muscle weakness. Patients with FSHD either have a contraction of the D4Z4 repeat on chromosome 4q35 or mutations in D4Z4 chromatin modifiers SMCHD1 and DNMT3B, both causing D4Z4 chromatin relaxation and inappropriate expression of the D4Z4-encoded DUX4 gene in skeletal muscle. In this study, we tested the hypothesis whether LRIF1, a known SMCHD1 protein interactor, is a disease gene for idiopathic FSHD2.MethodsClinical examination of a patient with idiopathic FSHD2 was combined with pathologic muscle biopsy examination and with genetic, epigenetic, and molecular studies.ResultsA homozygous LRIF1 mutation was identified in a patient with a clinical phenotype consistent with FSHD. This mutation resulted in the absence of the long isoform of LRIF1 protein, D4Z4 chromatin relaxation, and DUX4 and DUX4 target gene expression in myonuclei, all molecular and epigenetic hallmarks of FSHD. In concordance, LRIF1 was shown to bind to the D4Z4 repeat, and knockdown of the LRIF1 long isoform in muscle cells results in DUX4 and DUX4 target gene expression.ConclusionLRIF1 is a bona fide disease gene for FSHD2. This study further reinforces the unifying genetic mechanism, which postulates that FSHD is caused by D4Z4 chromatin relaxation, resulting in inappropriate DUX4 expression in skeletal muscle.

Abstract 278: The Glucocorticoid Receptor Antagonist RU486 Ameliorates Cold Stress-induced Exacerbation of Cardiac and Adipose Tissue Pathology and Metabolic Disorders in a Rat Model of Metabolic Syndrome

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Kai Nagasawa ◽  
Natsumi Matsuura ◽  
Yuji Minagawa ◽  
Shogo Ito ◽  
Yusuke Sano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Cold Stress ◽  
Rat Model ◽  
Metabolic Disorders ◽  
Glucose And Lipid Metabolism ◽  
Obese Rats ◽  
Antagonist Ru486

Introduction: Chronic stress, when combined with hyperphagia, can affect adiposity and metabolism. However, few studies have reported the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS). We investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology and gene expression and on glucose and lipid metabolism in a rat model of MetS. Methods and Results: We used DahlS.Z-Leprfa/Leprfa (DS/obese) rats which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a new animal model of MetS. DS/obese rats were exposed to cold stress (ice-cold water, 1 cm depth, 2 h/day) for 4 weeks beginning at 9 weeks of age with or without the GR antagonist RU486 (2 mg/kg/day, sc). Age-matched homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermates of DS/obese rats served as controls. Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction, in a manner sensitive to RU486. Cold stress and RU486 did not affect body weight or visceral and subcutaneous fat mass. In contrast, cold stress further increased superoxide production and NADPH oxidase activity in the heart as well as macrophage infiltration and the expression of proinflammatory genes in LV and visceral fat tissue. RU486 treatment inhibited these changes in gene expression, as well as cardiac oxidative stress and inflammation and adipose tissue inflammation. Cold stress further up-regulated cardiac renin-angiotensin-aldosterone system gene expression as well as the expression of GR and 11β-hydroxysteroid dehydrogenase type 1 genes in LV and visceral adipose tissue, and all of these effects were attenuated by RU486. In addition, RU486 ameliorated the stress-induced deterioration of dyslipidemia (elevations in low-density lipoprotein cholesterol, triglycerides, and free fatty acid) as well as that of glucose intolerance and insulin resistance. Conclusions: The present results indicate that GRs may be involved in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as that of glucose and lipid metabolism in a rat model of MetS.

scholarly journals GH signaling in human adipose and muscle tissue during ‘feast and famine’: amplification of exercise stimulation following fasting compared to glucose administration

2015 ◽  
Vol 173 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Mikkel H Vendelbo ◽  
Britt Christensen ◽  
Solbritt B Grønbæk ◽  
Morten Høgild ◽  
Michael Madsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Muscle Tissue ◽  
Target Gene ◽  
Exercise Bout ◽  
Metabolic Effects ◽  
Cytokine Signaling ◽  
Peripheral Tissues ◽  
Target Gene Expression ◽  
Gh Secretion

ObjectiveFasting and exercise stimulates, whereas glucose suppresses GH secretion, but it is uncertain how these conditions impact GH signaling in peripheral tissues. To test the original ‘feast and famine hypothesis’ by Rabinowitz and Zierler, according to which the metabolic effects of GH are predominant during fasting, we specifically hypothesized that fasting and exercise act in synergy to increase STAT-5b target gene expression.Design and methodsEight healthy men were studied on two occasions in relation to a 1 h exercise bout: i) with a concomitant i.v. glucose infusion (‘feast’) and ii) after a 36 h fast (‘famine’). Muscle and fat biopsy specimens were obtained before, immediately after, and 30 min after exercise.ResultsGH increased during exercise on both examination days and this effect was amplified by fasting, and free fatty acid (FFA) levels increased after fasting. STAT-5b phosphorylation increased similarly following exercise on both occasions. In adipose tissue, suppressors of cytokine signaling 1 (SOCS1) and SOCS2 were increased after exercise on the fasting day and both fasting and exercise increased cytokine inducible SH2-containing protein (CISH). In muscle, SOCS2 and CISH mRNA were persistently increased after fasting. Muscle SOCS1, SOCS3, and CISH mRNA expression increased, whereas SOCS2 decreased after exercise on both examination days.ConclusionsThis study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the ‘feast and famine hypothesis’; the adipose tissue signaling responses, which hitherto have not been scrutinized, may play a particular role in promoting FFA mobilization.

scholarly journals Ovariectomy in Mice Decreases Lipid Metabolism-Related Gene Expression in Adipose Tissue and Skeletal Muscle with Increased Body Fat

2005 ◽  
Vol 51 (2) ◽  
pp. 110-117 ◽  
Author(s):  
Yasutomi KAMEI ◽  
Miki SUZUKI ◽  
Hiromi MIYAZAKI ◽  
Nobuyo TSUBOYAMA-KASAOKA ◽  
Jian WU ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Body Fat ◽  
Related Gene

scholarly journals Removal of Epididymal Visceral Adipose Tissue Prevents Obesity-Induced Multi-organ Insulin Resistance in Male Mice

2021 ◽  
Vol 5 (5) ◽  
Author(s):  
Michael P Franczyk ◽  
Mai He ◽  
Jun Yoshino
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Visceral Adipose Tissue ◽  
Body Weight Gain ◽  
Whole Body ◽  
Atherogenic Dyslipidemia ◽  
Glucose And Lipid Metabolism ◽  
Visceral Adipose

Abstract Obesity is associated with insulin resistance, an important risk factor of type 2 diabetes, atherogenic dyslipidemia, and nonalcoholic fatty liver disease. The major purpose of this study was to test hypothesize that prophylactic removal of epididymal visceral adipose tissue (VAT) prevents obesity-induced multi-organ (liver, skeletal muscle, adipose tissue) insulin resistance. Accordingly, we surgically removed epididymal VAT pads from adult C57BL/6J mice and evaluated in vivo and cellular metabolic pathways involved in glucose and lipid metabolism following chronic high-fat diet (HFD) feeding. We found that VAT removal decreases HFD-induced body weight gain while increasing subcutaneous adipose tissue (SAT) mass. Strikingly, VAT removal prevents obesity-induced insulin resistance and hyperinsulinemia and markedly enhances insulin-stimulated AKT-phosphorylation at serine-473 (Ser473) and threonine-308 (Thr308) sites in SAT, liver, and skeletal muscle. VAT removal leads to decreases in plasma lipid concentrations and hepatic triglyceride (TG) content. In addition, VAT removal increases circulating adiponectin, a key insulin-sensitizing adipokine, whereas it decreases circulating interleukin 6, a pro-inflammatory adipokine. Consistent with these findings, VAT removal increases adenosine monophosphate–activated protein kinase C phosphorylation, a major downstream target of adiponectin signaling. Data obtained from RNA sequencing suggest that VAT removal prevents obesity-induced oxidative stress and inflammation in liver and SAT, respectively. Taken together, these findings highlight the metabolic benefits and possible action mechanisms of prophylactic VAT removal on obesity-induced insulin resistance and hepatosteatosis. Our results also provide important insight into understanding the extraordinary capability of adipose tissue to influence whole-body glucose and lipid metabolism as an active endocrine organ.

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