scholarly journals Impact of the Uncoupling Protein 1 on Cardiovascular Risk in Patients with Rheumatoid Arthritis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1131
Author(s):  
Lovisa I. Lyngfelt ◽  
Malin C. Erlandsson ◽  
Mitra Nadali ◽  
Shahram Hedjazifar ◽  
Rille Pullerits ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adipose Tissue ◽  
Cardiovascular Health ◽  
Uncoupling Protein ◽  
Serum Levels ◽  
High Plasma ◽  
High Serum ◽  
Uncoupling Protein 1 ◽  
Glucose Levels ◽  
Significant Difference

Adiposity is strongly associated with cardiovascular (CV) morbidity. Uncoupling protein 1 (UCP1) increases energy expenditure in adipocytes and may counteract adiposity. Our objective was to investigate a connection between UCP1 expression and cardiovascular health in patients with rheumatoid arthritis (RA) in a longitudinal observational study. Transcription of UCP1 was measured by qPCR in the subcutaneous adipose tissue of 125 female RA patients and analyzed with respect to clinical parameters and the estimated CV risk. Development of new CV events and diabetes mellitus was followed for five years. Transcription of UCP1 was identified in 89 (71%) patients. UCP1 positive patients had often active RA disease (p = 0.017), high serum levels of IL6 (p = 0.0025) and were frequently overweight (p = 0.015). IL-6hiBMIhi patients and patients treated with IL6 receptor inhibitor tocilizumab had significantly higher levels of UCP1 compared to other RA patients (p < 0.0001, p = 0.032, respectively). Both UCP1hi groups displayed unfavorable metabolic profiles with high plasma glucose levels and high triglyceride-to-HDL ratios, which indicated insulin resistance. Prospective follow-up revealed no significant difference in the incidence of new CV and metabolic events in the UCP1hi groups and remaining RA patients. The study shows that high transcription of UCP1 in adipose tissue is related to IL6-driven processes and reflects primarily metabolic CV risk in female RA patients.

Similar Serum Levels of IL-6 and its Soluble Receptors in Patients with HCV-Related Arthritis and Rheumatoid Arthritis: A Pilot Study

2012 ◽  
Vol 25 (1) ◽  
pp. 281-285 ◽  
Author(s):  
A. Riccio ◽  
L. Postiglione ◽  
P. Sabatini ◽  
M. Linvelli ◽  
I. Soriente ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Pilot Study ◽  
Healthy Subjects ◽  
Serum Levels ◽  
High Serum ◽  
Control Group ◽  
Serum Concentrations ◽  
Soluble Receptors ◽  
Significant Difference

The high serum levels of Interleukin-6 (IL-6) and its soluble receptors (sIL-6r and sgp 130), described in the course of Rheumatoid Arthritis (RA), have been linked to the enhanced activity of this cytokine in this disorder. In this study, the serum concentrations of IL-6 and its soluble receptors were determined in a group of patients with HCV-related arthritis (HCVrA), a condition resembling RA in several aspects, and then compared to those found in a sample of subjects affected by RA. Twenty-one patients with HCVrA, 24 patients with RA and 20 healthy subjects (control group) were examined. Different ELISA methods were used for determination of serum concentrations of IL-6, sIL-6r and sgp 130. Increased IL-6 serum levels were found in 15 (71%) of the patients with HCVrA and in 16 (62%) of those with RA. Eight (38%) of the patients with HCVrA and 11 (46%) of those with RA denoted high levels of sIL-6r, while sgp 130 levels were elevated in 21 (76%) of the patients with HCVrA and in 16 (69%) of those with RA. A significant difference between the median values of sIL-6r and sgp 130 levels in the two groups of patients versus controls was found. A mild correlation of these parameters with RF levels was detected in the RA group. Furthermore, in HCVrA patients the serum levels of IL-6, sIL-6r and sgpl30 appeared unrelated to HCV viraemia and to levels of transaminases. The enhanced serum levels of IL-6 in HCVra patients indicate an increased synthesis and hyperactivity of this cytokine in HCVrA, and the substantial similarity of the behaviour of IL-6 and its serum receptors in the two groups of patients suggests common mechanisms with RA, in which the function of IL-6 is central.

scholarly journals The Role of Uncoupling Protein 1 in the Metabolism and Adiposity of RIIβ-Protein Kinase A-Deficient Mice

2004 ◽  
Vol 18 (9) ◽  
pp. 2302-2311 ◽  
Author(s):  
Michael A. Nolan ◽  
Maria A. Sikorski ◽  
G. Stanley McKnight
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Kinase A

Abstract Mice lacking the RIIβ regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RIIβ−/− mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RIIβ null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RIIβ and UCP1 (RIIβ−/−/Ucp1−/−) were created, and the key parameters of metabolism and body composition were studied. We discovered that RIIβ−/− mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RIIβ−/− mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RIIβ null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RIIβ mutant mice.

Opposite Effects of Voluntary Physical Exercise on β3-Adrenergic Receptors in the White and Brown Adipose Tissue

2019 ◽  
Vol 51 (09) ◽  
pp. 608-617 ◽  
Author(s):  
Lucia Balagova ◽  
Jan Graban ◽  
Agnesa Puhova ◽  
Daniela Jezova
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Uncoupling Protein ◽  
Control Diet ◽  
Tryptophan Depletion ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Exercise Induced

AbstractCatecholamine effects via β3-adrenergic receptors are important for the metabolism of the adipose tissue. Physical exercise is a core component of antiobesity regimens. We have tested the hypothesis that voluntary wheel running results in enhancement of β3-adrenergic receptor gene expression in the white and brown adipose tissues. The secondary hypothesis is that dietary tryptophan depletion modifies metabolic effects of exercise. Male Sprague-Dawley rats were assigned for sedentary and exercise groups with free access to running wheels for 3 weeks. All animals received normal control diet for 7 days. Both groups were fed either by low tryptophan (0.04%) diet or by control diet (0.2%) for next 2 weeks. The β3-adrenergic receptor mRNA levels in response to running increased in the retroperitoneal and epididymal fat pads. The gene expression of uncoupling protein-1 (UCP-1) was increased in the brown, while unchanged in the white fat tissues. Unlike control animals, the rats fed by low tryptophan diet did not exhibit a reduction of the white adipose tissue mass. Tryptophan depletion resulted in enhanced concentrations of plasma aldosterone and corticosterone, but had no influence on exercise-induced adrenal hypertrophy. No changes in β3-adrenergic receptor and cell proliferation measured by 5-bromo-2′-deoxyuridine incorporation in left heart ventricle were observed. The reduced β3-adrenergic receptor but not enhanced uncoupling protein-1 gene expression supports the hypothesis on hypoactive brown adipose tissue during exercise. Reduction in dietary tryptophan had no major influence on the exercise-induced changes in the metabolic parameters measured.

Effects of intravenous isoproterenol (β-agonist) administration on expression and synthesis of ovine uncoupling protein-1

1999 ◽  
Vol 1999 ◽  
pp. 164-164
Author(s):  
D.S. Finn ◽  
P. Trayhurn ◽  
J. Struthers ◽  
M.A. Lomax
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Neonatal Life ◽  
Adrenoceptor Agonist ◽  
Brown Adipose

A crucial factor in the prevention of hypothermia in the neonatal lamb is the functional activitation of a mitochondrial uncoupling protein (UCP1) in brown adipose tissue. UCP1 disappears from lamb brown fat over the first 14 days of life (Finn et al., 1998), but it is not known whether this process can be modulated in lambs by the release of catecholamines which have been established in rodents as a mediator of the response to cold stress. This study examines the effect of administering a β-adrenoceptor agonist on the disappearance of UCP1 and UCP1 mRNA during early neonatal life, using immunohistochemistry and in situ hybridization.

scholarly journals Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases

2020 ◽  
Vol 21 (4) ◽  
pp. 1219 ◽  
Author(s):  
Hyung Muk Choi ◽  
Hari Madhuri Doss ◽  
Kyoung Soo Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Metabolic Disorders ◽  
Serum Levels ◽  
High Serum ◽  
Low Molecular Weight ◽  
High Serum Level ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular, middle-molecular, and low-molecular weight isoforms. Numerous studies have demonstrated its insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects. Additionally, decreased serum levels of adiponectin is associated with chronic inflammation of metabolic disorders including Type 2 diabetes, obesity, and atherosclerosis. However, recent studies showed that adiponectin could have pro-inflammatory roles in patients with autoimmune diseases. In particular, its high serum level was positively associated with inflammation severity and pathological progression in rheumatoid arthritis, chronic kidney disease, and inflammatory bowel disease. Thus, adiponectin seems to have both pro-inflammatory and anti-inflammatory effects. This indirectly indicates that adiponectin has different physiological roles according to an isoform and effector tissue. Knowledge on the specific functions of isoforms would help develop potential anti-inflammatory therapeutics to target specific adiponectin isoforms against metabolic disorders and autoimmune diseases. This review summarizes the current roles of adiponectin in metabolic disorders and autoimmune diseases.

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