Subsets of human type 2 macrophages show differential capacity to produce reactive oxygen species

2013 ◽  
Vol 284 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Marina D. Kraaij ◽  
Karin M. Koekkoek ◽  
Sandra W. van der Kooij ◽  
Kyra A. Gelderman ◽  
Cees van Kooten
Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 923-933 ◽  
Author(s):  
Theresa Schöttl ◽  
Lisa Kappler ◽  
Katharina Braun ◽  
Tobias Fromme ◽  
Martin Klingenspor

Abstract Accumulation of visceral fat is associated with metabolic risk whereas excessive amounts of peripheral fat are considered less problematic. At the same time, altered white adipocyte mitochondrial bioenergetics has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. We therefore investigated whether the metabolic risk of visceral vs peripheral fat coincides with a difference in mitochondrial capacity of white adipocytes. We assessed bioenergetic parameters of subcutaneous inguinal and visceral epididymal white adipocytes from male C57BL/6N mice employing a comprehensive respirometry setup of intact and permeabilized adipocytes as well as isolated mitochondria. Inguinal adipocytes clearly featured a higher respiratory capacity attributable to increased mitochondrial respiratory chain content compared with epididymal adipocytes. The lower capacity of mitochondria from epididymal adipocytes was accompanied by an increased generation of reactive oxygen species per oxygen consumed. Feeding a high-fat diet (HFD) for 1 week reduced white adipocyte mitochondrial capacity, with stronger effects in epididymal when compared with inguinal adipocytes. This was accompanied by impaired body glucose homeostasis. Therefore, the limited bioenergetic performance combined with the proportionally higher generation of reactive oxygen species of visceral adipocytes could be seen as a candidate mechanism mediating the elevated metabolic risk associated with this fat depot.


2009 ◽  
Vol 2 (5) ◽  
pp. 317-321 ◽  
Author(s):  
Camila Armond Isoni ◽  
Érica Abreu Borges ◽  
Clara Araújo Veloso ◽  
Rafael Teixeira Mattos ◽  
Miriam Martins Chaves ◽  
...  

Peripheral blood mononuclear cells (PBMNC) from patients with type 2 diabetes (DM2) have generated higher levels of reactive oxygen species (ROS) that were higher than those in cells from healthy individuals. In the presence of a cAMP-elevating agent, ROS production was significantly activated in PBMNC from DM2 patients but it was inhibited in cells from healthy subjects. Higher levels of IL-6 has been detected in the supernatant of PBMNC cultures from DM2 patients in comparison with healthy controls. When cells were cultured in the presence of a cAMP-elevating agent, the level of IL-6 decreased has by 46% in the supernatant of PBMNC from DM2 patients but it remained unaltered in controls. No correlations between ROS and IL-6 levels in PBMNC from DM2 patients or controls have been observed. Secretions of IL-4 or IFN by PBMNC from patients or controls have not been affected by the elevation of cAMP. cAMP elevating agents have activated the production of harmful reactive oxidant down modulated IL-6 secretion by these cells from DM2 patients, suggesting an alteration in the metabolic response possibly due to hyperglicemia. The results suggest that cAMP may play an important role in the pathogenesis of diabetes.


2016 ◽  
Vol 17 (1) ◽  
pp. 35-41
Author(s):  
Nevena Gajovic ◽  
Ivan Jovanovic ◽  
Aleksandar Ilic ◽  
Nevena Jeremic ◽  
Vladimir Jakovljevic ◽  
...  

Abstract Diabetes mellitus is chronic disorder characterized by hyperglycaemia. Hyperglycaemia induces mitochondrial dysfunction, enhances oxidative stress and thus promotes reactive oxygen species (ROS) production. Earlier studies suggested that reactive oxygen species (ROS) are involved in the pathogenesis of many diseases. Previous studies have revealed that hyperglycaemia changes the functional phenotype of monocytes, macrophages, neutrophils, NK cells and CD8+ T cells. The aim of this study was to investigate whether diabetes affects the functional phenotype of NKT cells. Diabetes mellitus was induced in BALB/c mice by intraperitoneal injection of streptozotocin at a single dose of 170 mg/kg body weight. The number and functional phenotype of splenic NKT cells was assessed by fl ow cytometry, 28 days after diabetes induction. The diabetic condition facilitated the production of antioxidant enzymes, including catalase (p<0.05) and superoxide dismutase. Hyperglycaemia enhanced oxidative stress and thus decreased the number of splenic NKT cells but did not change the percentage of splenic CD3+CD49+ NKT cells that express the activatory receptor NKP46 or produce IFN-γ. However, hyperglycaemia increased the frequency of splenic NKT cells that express KLRG-1 and produce TGF-β, IL-4, and IL-5, and it decreased the frequency of IL-17+ NKT cells. Our study indicates that diabetes mellitus induces oxidative stress and switches the functional phenotype of NKT cells towards type 2 (IL-4 and IL-5 producing NKTs) and regulatory (TGF-β Thproducing NKTs) phenotypes. These findings are correlated with the clinical observation in humans that diabetic patients are more prone to infections and tumours.


2021 ◽  
Author(s):  
Yingying Li ◽  
Hai Wang ◽  
Yuan Liao ◽  
Quanmei Yan ◽  
Zhen Ouyang ◽  
...  

Abstract Obesity is one of the most important risk factors for type 2 diabetes (T2DM). The CREBRF missense allele of rs373863828 (p.Arg457Gln) is associated with increased body mass index (BMI), yet reduced risk of T2DM in people with Pacific ancestry. To investigate the functional consequences of the CREBRF variant, we introduced the corresponding human mutation p.Arg457Gln into porcine genome by using a CRISPR/Cas9-mediated homologous recombination (HR)-dependent approach. The CREBRF p.Arg457Gln pig models displayed dramatically increased fat deposition, yet improved sensitivity to insulin. Transcriptome and metabolome analyses of subcutaneous white adipose tissues showed that the CREBRF p.Arg457Gln mutation promoted preadipocyte differentiation, which indicated that obesity was caused by increased number (hyperplasia) rather than size (hypertrophy) of adipocytes. In addition, the oxidative capacity decreased in the adipose tissue of pigs with CREBRF p.Arg457Gln variant. The pre-oxidative metabolite content (4-HNE and MDA) significantly decreased, while activity of antioxidant enzymes (GPX, SOD, and CAT) increased, thereby repressing oxidative metabolism of adipose tissue and reducing level of reactive oxygen species (ROS). The low reactive oxygen species could prevent insulin resistance and reduce risk of obesity-induced type 2 diabetes. This study provides further mechanistic insights into favourable adiposity resulting from CREBRF p.Arg457Gln.


2014 ◽  
Vol 306 (11) ◽  
pp. H1558-H1568 ◽  
Author(s):  
Saisudha Koka ◽  
Hema S. Aluri ◽  
Lei Xi ◽  
Edward J. Lesnefsky ◽  
Rakesh C. Kukreja

Enhanced nitric oxide (NO) production is known to activate silent information regulator 1 (SIRT1), which is a histone deacetylase that regulates PGC-1α, a regulator of mitochondrial biogenesis and coactivator of transcription factors impacting energy homeostasis. Since phosphodiesterase-5 inhibitors potentiate NO signaling, we hypothesized that chronic treatment with phosphodiesterase-5 inhibitor tadalafil would activate SIRT1-PGC-1α signaling and protect against metabolic stress-induced mitochondrial dysfunction in diabetic hearts. Diabetic db/db mice ( n = 32/group; 40 wk old) were randomized to receive DMSO (10%, 0.2 ml ip) or tadalafil (1 mg/kg ip in 10% DMSO) for 8 wk. Wild-type C57BL mice served as nondiabetic controls. The hearts were excised and homogenized to study SIRT1 activity and downstream protein targets. Mitochondrial function was determined by measuring oxidative phosphorylation (OXPHOS), and reactive oxygen species generation was studied in isolated mitochondria. Tadalafil-treated diabetic mice demonstrated significantly improved left ventricular function, which is associated with increased cardiac SIRT1 activity. Tadalafil also enhanced plasma NO oxidation levels, myocardial SIRT1, PGC-1α expression, and phosphorylation of eNOS, Akt, and AMPK in the diabetic hearts. OXPHOS with the complex I substrate glutamate was decreased by 50% in diabetic hearts compared with the nondiabetic controls. Tadalafil protected OXPHOS with an improved glutamate state 3 respiration rates. The increased reactive oxygen species production from complex I was significantly decreased by tadalafil treatment. In conclusion, chronic treatment with tadalafil activates NO-induced SIRT1-PGC-1α signaling and attenuates mitochondrial dysfunction in type 2 diabetic hearts.


Diabetologia ◽  
2009 ◽  
Vol 52 (4) ◽  
pp. 574-582 ◽  
Author(s):  
M. A. Abdul-Ghani ◽  
R. Jani ◽  
A. Chavez ◽  
M. Molina-Carrion ◽  
D. Tripathy ◽  
...  

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