Betaine reduces the expression of inflammatory adipokines caused by hypoxia in human adipocytes

2012 ◽  
Vol 109 (1) ◽  
pp. 43-49 ◽  
Author(s):  
K. Olli ◽  
S. Lahtinen ◽  
N. Rautonen ◽  
K. Tiihonen
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Markers ◽  
Mrna Level ◽  
Low Grade ◽  
Human Adipocytes ◽  
Low Oxygen ◽  
Hypoxic Conditions ◽  
Tnf Α ◽  
Oxygen Conditions ◽  
Low Grade Inflammation

Obesity is characterised by a state of chronic low-grade inflammation and the elevated circulating and tissue levels of inflammatory markers, including inflammation-related adipokines, released from white adipose tissue. The expression and release of these adipokines generally rises as the adipose tissue expands and hypoxic conditions start to develop within the tissue. Here, the effect of betaine, a trimethylglycine having a biological role as an osmolyte and a methyl donor, on the expression of inflammation-related markers was tested in human adipocytes under hypoxia. Differentiated adipocytes were cultivated under low (1 %) oxygen tension for 8–20 h. The expression of different adipokines, including IL-6, leptin, PPARγ, TNF-α and adiponectin, was measured by quantitative PCR by determining the relative mRNA level from the adipocytes. Hypoxia, in general, led to a decrease in the expression of PPARγ mRNA in human adipocytes, whereas the expression levels of leptin and IL-6 mRNA were substantially increased by hypoxia. The cultivation of adipocytes under hypoxia also led to a reduction in the expression of TNF-α mRNA. The results showed that hypoxia increased the relative quantification of leptin gene transcription, and that betaine (250 μmol/l) reduced this effect, caused by low oxygen conditions. Under hypoxia, betaine also reduced the mRNA level of the pro-inflammatory markers IL-6 and TNF-α. These results demonstrate that the extensive changes in the expression of inflammation-related adipokines in human adipocytes caused by hypoxia can be diminished by the presence of physiologically relevant concentrations of betaine.

Role of the adipocyte-specific NF-κB activity in the regulation of IP-10 and T cell migration

2011 ◽  
Vol 300 (2) ◽  
pp. E304-E311 ◽  
Author(s):  
Patricia Krinninger ◽  
Cornelia Brunner ◽  
Pedro A. Ruiz ◽  
Elisabeth Schneider ◽  
Nikolaus Marx ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cell Migration ◽  
T Cell ◽  
Interferon Γ ◽  
Low Grade ◽  
Human Adipocytes ◽  
Migration Assay ◽  
T Cell Migration ◽  
Low Grade Inflammation

Infiltration of immune cells into adipose tissue plays a central role in the pathophysiology of obesity-associated low-grade inflammation. The aim of this study was to analyze the role of adipocyte NF-κB signaling in the regulation of the chemokine/adipokine interferon-γ-induced protein 10 kDa (IP-10) and adipocyte-mediated T cell migration. Therefore, the regulation of IP-10 was investigated in adipose tissue of male C57BL/6J mice, primary human and 3T3-L1 preadipocytes/adipocytes. To specifically block the NF-κB pathway, 3T3-L1 cells stably overexpressing a transdominant mutant of IκBα were generated, and the chemical NF-κB inhibitor Bay117082 was used. Adipocyte-mediated T cell migration was assessed by a migration assay. It could be shown that IP-10 expression was higher in mature adipocytes compared with preadipocytes. Induced IP-10 expression and secretion were completely blocked by an NF-κB inhibitor in 3T3-L1 and primary human adipocytes. Stable overexpression of a transdominant mutant of IκBα in 3T3-L1 adipocytes led to an inhibition of basal and stimulated IP-10 expression and secretion. T cell migration was induced by 3T3-L1 adipocyte-conditioned medium, and both basal and induced T cell migration was strongly inhibited by stable overexpression of a transdominant IκBα mutant. In addition, with the use of an anti-IP-10 antibody, a significant decrease of adipocyte-induced T cell migration was shown. In conclusion, in this study, we could demonstrate that the NF-κB pathway is essential for the regulation of IP-10 in 3T3-L1 and primary human adipocytes. Adipocytes rather than preadipocytes contribute to NF-κB-dependent IP-10 expression and secretion. Furthermore, NF-κB-dependent factors and especially IP-10 represent novel signals from adipocytes to induce T cell migration.

scholarly journals Lipopolysaccharide influence on leptin hormone and tumor necrosis factor-alpha release from human adipose tissue

2018 ◽  
Vol 16 ◽  
pp. 205873921877497
Author(s):  
Sa’ad Al-Lahham ◽  
Nidal Jaradat ◽  
Malik Al-Qub ◽  
Abdallah Hamayel ◽  
Abdalrahman Assaassa ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Low Grade Inflammation ◽  
Necrosis Factor

Obesity is associated with low-grade inflammation that originates mainly from adipose tissue. This is implicated in the pathogenesis of type-2 diabetes and cardiovascular diseases. Strong evidence indicates that chronically elevated systemic low-grade lipopolysaccharide (LPS), elicits low-grade inflammation. However, evidence on LPS effect on adipokines’ level, such as leptin, is scarce, and it has never been investigated ex vivo in human subcutaneous adipose tissue (SAT) and therefore we aim to investigate this. To achieve our aim, SAT explants were obtained from 12 patients (50% males) and were treated with/without LPS. Protein concentration was determined by enzyme-linked immunosorbent assay (ELISA). We found that the average age and body mass index (BMI) of included patients were 58.6 years and 28.6 kg/m2, respectively. LPS induced significantly (~3×, P < 0.0001) the secretion of tumor necrosis factor (TNF)-α from SAT, and it was not associated with age or BMI. However, leptin secretion was inhibited slightly (~20%), but significantly. Interestingly, leptin release was significantly inhibited (~50%) in SAT from lean but not from obese patients, and there was an association between leptin response and BMI (R = 0.8), but no association with age. In this study, we found, for the first time, that LPS suppresses the release of leptin hormone from SAT obtained from lean patients, while it induces TNF-α release. Our findings provide extra evidence and confirm earlier studies regarding the role of LPS in low-grade inflammation. Further investigations are essential to identify factors that inhibit LPS passage through intestinal barrier in order to prevent or reduce the development of obesity and its associated chronic diseases.

Waist-to-height ratio as a marker of low-grade inflammation in obese children and adolescents

2016 ◽  
Vol 29 (5) ◽  
Author(s):  
Carolina Caminiti ◽  
Marisa Armeno ◽  
Carmen S. Mazza
Keyword(s):  
Logistic Regression ◽  
Children And Adolescents ◽  
Inflammatory Markers ◽  
Low Grade ◽  
Obese Children ◽  
Height Ratio ◽  
Metabolic Complications ◽  
Tnf Α ◽  
Waist To Height Ratio ◽  
Low Grade Inflammation

AbstractThe epidemic of childhood obesity is associated with early atherosclerosis. Several reports have related this event to low-grade inflammation described in obesity. CRP and IL6 are markers that correlate with adiposity. The waist-to-height ratio (WtHR) is an anthropometric marker associated with insulin resistance and inflammation. The objective of this study was to assess the correlation between WtHR, metabolic complications and pro-inflammatory factors in obese children and adolescents.Weight, height, waist circumference, glycemia, insulin, CRP, TNF-α and IL-6 were measured in the baseline sample in 280 patients 6–19 years of age with overweight or obesity (OW/OB) and 112 normal-weight controls. Logistic regression was performed using WtHR as an independent variable. p>0.05 STATA11.Mean WtHR was 0.6±0.06 in OW/OB and 0.43±0.02 in controls (p<0.01). WtHR was increased in 93% of the OW/OB vs. 2% of the controls. In the OW/OB inflammatory markers were significantly increased (p<0.01) compared to the controls (CRP 2.2 vs. 0.8; Il-6 2.9 vs. 2.1; and TNF-α 6.2 vs. 5.5). In the WtHR>0.5, insulin resistence and inflammatory markers were significantly increased (p<0.01) compared to the WtHR<0.5 (HOMA 3.4 vs. 1.4; CRP 2.3 vs. 0.6; Il-6 2.9 vs. 2.1; and TNF-α 6.4 vs. 5.55). In logistic regression, a significant independent association was found between WtHR with CRP (OR1.47), IL6 (OR1.60) and TNF-α (OR1.79).Obese children and adolescents have high inflammatory markers that may increase cardiovascular risk. WtHR is associated with low-grade inflammation and may be considered a relevant anthropometric marker in the clinical practice.

Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?

2015 ◽  
Vol 113 (9) ◽  
pp. 1355-1364 ◽  
Author(s):  
Zhen He ◽  
Min Li ◽  
Dongmei Zheng ◽  
Qing Chen ◽  
Wenwen Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Hypoxia Inducible Factor ◽  
Ethanol Consumption ◽  
Oral Glucose ◽  
Low Grade ◽  
Tnf Α ◽  
Low Grade Inflammation

The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects

2006 ◽  
Vol 290 (5) ◽  
pp. E961-E967 ◽  
Author(s):  
Jens M. Bruun ◽  
Jørn W. Helge ◽  
Bjørn Richelsen ◽  
Bente Stallknecht
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Inflammatory Markers ◽  
Macrophage Infiltration ◽  
Hypocaloric Diet ◽  
Low Grade ◽  
Severely Obese ◽  
Obese Subjects ◽  
Low Grade Inflammation

Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight ( P < 0.001) and increased insulin sensitivity (homeostasis model assessment; P < 0.05). Plasma adiponectin ( P < 0.001) increased, and C-reactive protein ( P < 0.05), IL-6 ( P < 0.01), IL-8 ( P < 0.05), and monocyte chemoattractant protein-1 ( P < 0.01) decreased. AT inflammation was reduced, determined from an increased mRNA expression of adiponectin ( P < 0.001) and a decreased expression of macrophage-specific markers (CD14, CD68), IL-6, IL-8, and tumor necrosis factor-α ( P < 0.01). After adjusting for macrophage infiltration in AT, only IL-6 mRNA was decreased ( P < 0.05). Only very low levels of inflammatory markers were found in SM. The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM. Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low-grade inflammation. Markers of inflammation were particularly reduced in AT, whereas SM does not contribute to this attenuation of whole body inflammation.

The Role of Epicardial Adipose Tissue Lymphocytes in Low-Grade Inflammation and Coronary Artery Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 469-P
Author(s):  
MILOS MRAZ ◽  
ANNA CINKAJZLOVA ◽  
ZDENA LACINOVÁ ◽  
JANA KLOUCKOVA ◽  
HELENA KRATOCHVILOVA ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Epicardial Adipose Tissue ◽  
Low Grade ◽  
Artery Disease ◽  
Low Grade Inflammation

scholarly journals Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Charmaine S. Tam ◽  
Leanne M. Redman
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Proinflammatory Mediators ◽  
Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

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