scholarly journals Irisin Is Regulated by CAR in Liver and Is a Mediator of Hepatic Glucose and Lipid Metabolism

2016 ◽  
Vol 30 (5) ◽  
pp. 533-542 ◽  
Author(s):  
Li Mo ◽  
Jing Shen ◽  
Qinhui Liu ◽  
Yuwei Zhang ◽  
Jiangying Kuang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Uncoupling Protein ◽  
Constitutive Androstane Receptor ◽  
Physiological Role ◽  
Glucose And Lipid Metabolism ◽  
Diet Induced Obesity ◽  
Fibronectin Type Iii ◽  
Glucose And Lipid Homeostasis ◽  
Fibronectin Type Iii Domain ◽  
Amp Activated Protein Kinase

Abstract Irisin, a hormone proteolytically processed from fibronectin type III domain-containing protein 5 (FNDC5), has been reported to induce the browning of sc adipocytes by increasing the level of uncoupling protein 1. In this study, we showed that activation of the nuclear receptor constitutive androstane receptor induced FNDC5 mRNA expression in the liver and increased the circulating level of irisin in mice. FNDC5/irisin is a direct transcriptional target of constitutive androstane receptor. Hepatic-released irisin functioned as a paracrine/autocrine factor that inhibited lipogenesis and gluconeogenesis via the Adenosine 5′-monophosphate (AMP)-activated protein kinase pathway. Adenovirus-overexpressed irisin improved hepatic steatosis and insulin resistance in genetic-induced obese mice. Irisin transgenic mice were also protected against high-fat diet-induced obesity and insulin resistance. In conclusion, our results reveal a novel pathway in regulating FNDC5/irisin expression and identify a physiological role for this hepatic hormone in glucose and lipid homeostasis.

scholarly journals Exposure to the Widely Used Pyrethroid Pesticide Deltamethrin, Does Not Exacerbate High Fat Diet Induced Obesity or Insulin Resistance in C57BL/6J Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A45-A46
Author(s):  
Evangelia Evelyn Tsakiridis ◽  
Marisa Morrow ◽  
Andrea Llanos ◽  
Bo Wang ◽  
Alison Holloway ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glycemic Control ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Pyrethroid Pesticide ◽  
First Time

Abstract Deltamethrin is a commonly used pesticide for the control of mosquito populations. Despite widespread use, the effects of deltamethrin on adiposity and glucose homeostasis have been equivocal with some studies showing increased, decreased and no effect on adiposity and glycemic control. However, no study to date has investigated the effect of deltamethrin in mice housed at thermoneutral temperatures, which is important for modelling metabolic diseases in rodents due to reduced thermal stress and constitutive activation of brown adipose tissue. In the current study we demonstrate for the first time that deltamethrin reduces uncoupling protein-1 expression in brown adipocytes cultured in vitro at concentrations as low as 1pm. Meanwhile, in-vivo deltamethrin does not appear to alter glycemic control or promote adiposity at exposures equivalent to 0.01, 0.1 or 1.0 mg/kg/day. Together, our study demonstrates environmentally relevant exposure to deltamethrin does not exacerbate diet induced obesity or insulin resistance.

scholarly journals Tissue factor pathways linking obesity and inflammation

2015 ◽  
Vol 35 (03) ◽  
pp. 279-283 ◽  
Author(s):  
F. Samad ◽  
W. Ruf
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Tissue Factor ◽  
Clinical Markers ◽  
Protease Activated Receptors ◽  
Diet Induced Obesity ◽  
The Metabolic Syndrome ◽  
Amp Activated Protein Kinase ◽  
G Protein Coupled

SummaryObesity is a major cause for a spectrum of metabolic syndrome-related diseases that include insulin resistance, type 2 diabetes, and steatosis of the liver. Inflammation elicited by macrophages and other immune cells contributes to the metabolic abnormalities in obesity. In addition, coagulation activation following tissue factor (TF) upregulation in adipose tissue is frequently found in obese patients and particularly associated with diabetic complications. Genetic and pharmacological evidence indicates that TF makes significant contributions to the development of the metabolic syndrome by signaling through G protein-coupled protease activated receptors (PARs). Adipocyte TF-PAR2 signaling contributes to diet-induced obesity by decreasing metabolism and energy expenditure, whereas hematopoietic TF-PAR2 signaling is a major cause for adipose tissue inflammation, hepatic steatosis and inflammation, as well as insulin resistance. In the liver of mice on a high fat diet, PAR2 signaling increases transcripts of key regulators of gluconeogenesis, lipogenesis and inflammatory cytokines. Increased markers of hepatic gluconeogenesis correlate with decreased activation of AMP-activated protein kinase (AMPK), a known regulator of these pathways and a target for PAR2 signaling. Clinical markers of a TF-induced prothrombotic state may thus indicate a risk in obese patient for developing complications of the metabolic syndrome.

scholarly journals The Role of Physical Exercise Intesity to Irisin Levels on Overweight and Obese

2021 ◽  
Vol 57 (4) ◽  
pp. 357
Author(s):  
Ido Nur Abdulloh ◽  
Sugiharto Sugiharto ◽  
Purwo Sri Rejeki
Keyword(s):  
Physical Exercise ◽  
Uncoupling Protein ◽  
Pharmacological Therapy ◽  
Mitogen Activated Protein Kinase ◽  
Amino Acid Residues ◽  
Mitogen Activated Protein ◽  
Fibronectin Type Iii ◽  
Obese Subjects ◽  
Fibronectin Type Iii Domain ◽  
The Right

Highlight:The differences in intensity physical exercise mechanisms associated with increased irisin secretion in overweight and obese subjects were determined.The secretion of irisin in the right intensity blood on obesity can be reduced because the calories were balanced. Abstract:Physical exercise is a non-pharmacological therapy that can secrete various types of myokines to treat obesity problems. One of the myokines that play a role is irisin. Irisin is a polypeptide hormone with 112 amino acid residues that are synthesized in skeletal muscle after the proteolytic precursor cleavage of fibronectin type III domain-containing protein 5 (FNDC5). The release of irisin in the blood circulation will stimulate the browning process in white fat tissue by inducing the expression of uncoupling protein-1 (UCP-1) through signaling p38 mitogen-activated protein kinase (p38-MAPK) to increase energy expenditure, thermogenesis and reduce fat accumulation. This study described the differences in intensity of physical exercise mechanisms associated with the increased irisin secretion in overweight and obese subjects. This study was designed as a literature review that involved studies from research journals in the last 10 years concerning humans from some databases, such as Science Direct, PubMed, and Google Scholar. This study also discussed the relationship between the intensity of physical exercise and the synthesis, secretion, circulation, and regulation of irisin in preventing obesity.

Auricular acupuncture induces FNDC5/irisin and attenuates obese inflammation in mice

2020 ◽  
Vol 38 (4) ◽  
pp. 264-271
Author(s):  
Yi Lu ◽  
Guohua Li
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Control Diet ◽  
Auricular Acupuncture ◽  
Acupuncture Points ◽  
Brown Adipose ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Factor Α ◽  
Old Mice

Objective: To investigate whether auricular acupuncture (AA) attenuates bodyweight and obese inflammation through the release of irisin from muscle tissue in mice. Methods: Sixty 4-week-old mice were fed a high fat diet (HFD) for 4 weeks. These animals were divided into six groups that remained untreated (HFD) or underwent electrical AA (HFD+EAA), sham EAA (HFD+SEAA), adrenalectomy (HFD+AD), adrenalectomy and EAA (HFD+AD+EAA), or adrenalectomy and injection of recombinant lentivirus expressing fibronectin type III domain-containing protein 5 (rFNDC) (HFD+AD+rFNDC) in the ninth week. The EAA and SEAA were performed at two traditional auricular acupuncture points daily for 4 weeks. An additional 10 mice fed a control diet were included as a normal control (NC) group. At the end of the study, norepinephrine (NE) in the serum, tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β) in the serum and white adipose tissue, irisin in the serum and muscle, uncoupling protein-1 (UCP-1) in the brown adipose tissue (BAT), and FNDC5 in the muscle, were analysed. Results: The AD+EAA group exhibited better control of bodyweight and inflammation compared with the AD+SEAA and untreated HFD model groups (P<0.05), especially regarding the increased expression of NE, FNDC5, irisin and UCP-1 (P<0.05). After adrenalectomy, mice receiving EAA had less NE, FNDC5, irisin and UCP-1 as well as greater expression of inflammatory cytokines and bodyweight. However, lentiviral overexpression of rFNDC successfully reversed this situation in the AD mice and mimicked the effects of EAA on bodyweight, inflammation and expression of FNDC5, irisin and UCP-1, although it did not impact NE. Conclusions: EAA promoted NE release from the adrenal gland leading to further expression of FNDC5, irisin and UCP-1, which contributed to weight management and inflammatory inhibition.

scholarly journals Uncoupling protein 1 expression does not protect mice from diet-induced obesity

2020 ◽  
Author(s):  
Hui Wang ◽  
Monja Willershäuser ◽  
Yongguo Li ◽  
Tobias Fromme ◽  
Katharina Schnabl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Physiological Role ◽  
Metabolic Phenotype ◽  
Daily Injection ◽  
Diet Induced Obesity ◽  
Reporter Mice ◽  
Ucp1 Expression

We studied the metabolic phenotype of a novel Ucp1-LUC-iRFP713 knock-in reporter gene mouse model originally generated to monitor endogenous Ucp1 gene expression. Both reporter mice and reporter cells reliably reflected Ucp1 gene expression in vivo and in vitro. We here report an unexpected reduction in UCP1 content in homozygous knock-in (KI) reporter mice. As a result, the thermogenic capacity of KI mice stimulated by norepinephrine was largely blunted, making them more sensitive to an acute cold exposure. In return, these reporter mice with reduced UCP1 expression enabled us to investigate the physiological role of UCP1 in the prevention of weight gain. We observed no substantial differences in body mass across the three genotypes, irrespective of the type of diet or the ambient temperature, possibly due to the insufficient UCP1 activation. Indeed, activation of UCP1 by daily injection of the selective β3-adrenergic receptor agonist CL316,243 resulted in significantly greater reduction of body weight in WT mice than in KI mice. Taken together, we conclude that the intact expression of UCP1 is essential for cold-induced thermogenesis but the presence of UCP1 per se does not protect mice from diet-induced obesity.

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