Nejvíce citovaný článek - PubMed ID 15864338
The contribution of environmental pollutants to the obesity pandemic is still not yet fully recognized. Elucidating possible cellular and molecular mechanisms of their effects is of high importance. Our study aimed to evaluate the effect of chronic, 21-day-long, 2,2-bis (4-chlorophenyl)-1,1-dichlorethylenedichlorodiphenyldichloroethylene (p,p'-DDE) exposure of human adipose-derived mesenchymal stem cells committed to adipogenesis on mitochondrial oxygen consumption on days 4, 10, and 21. In addition, the mitochondrial membrane potential (MMP), the quality of the mitochondrial network, and lipid accumulation in maturing cells were evaluated. Compared to control differentiating adipocytes, exposure to p,p'-DDE at 1 μM concentration significantly increased basal (routine) mitochondrial respiration, ATP-linked oxygen consumption and MMP of intact cells on day 21 of adipogenesis. In contrast, higher pollutant concentration seemed to slow down the gradual increase in ATP-linked oxygen consumption typical for normal adipogenesis. Organochlorine p,p'-DDE did not alter citrate synthase activity. In conclusion, in vitro 1 μM p,p'-DDE corresponding to human exposure is able to increase the mitochondrial respiration per individual mitochondrion at the end of adipocyte maturation. Our data reveal that long-lasting exposure to p,p'-DDE could interfere with the metabolic programming of mature adipocytes.
- Klíčová slova
- adipogenesis, human adipose-derived mesenchymal stem cells, mitochondrial respiration, p,p′-DDE,
- MeSH
- adipogeneze účinky léků MeSH
- buněčná diferenciace účinky léků MeSH
- dichlordifenyldichlorethylen toxicita MeSH
- kultivované buňky MeSH
- látky znečišťující životní prostředí toxicita MeSH
- lidé MeSH
- membránový potenciál mitochondrií MeSH
- mezenchymální kmenové buňky cytologie účinky léků MeSH
- mitochondrie účinky léků MeSH
- obezita metabolismus MeSH
- tukové buňky cytologie účinky léků MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dichlordifenyldichlorethylen MeSH
- látky znečišťující životní prostředí MeSH
BACKGROUND: The aim of the study was to analyze the degree of obesity and its associations with age, gender, inflammation, an estimated glomerular filtration rate (eGFR), and liver function in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 874 consecutive adult Caucasian T2DM patients from outpatient diabetic clinic were included in the study. The relative fat mass (RFM) and body mass index (BMI) were used as obesity markers. Serum creatinine and cystatin C were used for the GFR estimation. Serum high-sensitive C-reactive protein (hsCRP) was used as the indicator of inflammation. RESULTS: The median, interquartile range (IQR) of RFM in females was higher than that in males (44.8 (42.3-47.2) % vs 31.3 (28.8-34.1) %, respectively; P < .0001). The median (IQR) of BMI in females was no higher than that in males (30 (27-34) kg/m2 vs 30 (27-34), respectively; P = .5152). The obesity prevalence was 99% in males and 98% in females according to RFM. BMI recognized obesity in 51% males and 53% females. RFM was positively associated with hsCRP in both males (rs = .296, P < .0001) and females (rs = .445, P < .0001). ALT was positively correlated with eGFRcys in both males (rs = .379, P < .0001) and females (rs = .308, P < .0001). CONCLUSION: The RFM equation leads to higher obesity prevalence compared to BMI. Women have higher RFM compared to men. The kidney function was positively correlated with ALT serum concentrations.
- Klíčová slova
- abdominal fat, adipose tissue, alanine transaminase, body mass index, cystatin C, diabetes mellitus, glomerular filtration rate, inflammation, kidney diseases, obesity,
- MeSH
- C-reaktivní protein analýza MeSH
- chronická renální insuficience etiologie patofyziologie MeSH
- diabetes mellitus 2. typu komplikace patofyziologie MeSH
- hodnoty glomerulární filtrace * MeSH
- index tělesné hmotnosti MeSH
- jaterní testy MeSH
- lidé středního věku MeSH
- lidé MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tuková tkáň * patofyziologie MeSH
- zánět etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- C-reaktivní protein MeSH
BACKGROUND: Obesity is a known high-risk factor for the development of vascular diseases and chronic kidney disease (CKD). In this study we aimed to elucidate the impact of adipose tissue on the inflammatory state in CDK patients with obesity. PATIENTS AND METHODS: A cohort of 40 patients with CKD (stages 3-4) with mild proteinuria (2.3-3.5 g/day) were analyzed in a prospective cross-sectional study: single blood samples and visceral and subcutaneous samples of adipose tissue were taken from 20 patients with obesity and 20 without obesity (control group) during elective abdominal surgery (laparoscopic cholecystectomy). Serum concentrations of asymmetric dimethylarginine (ADMA), adiponectin, C-reactive protein, interleukin-6, tumor necrosis factor-alpha, pentosidine and monocyte chemoattractant protein-1 were measured. Messenger RNA expression of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, adiponectin receptors 1 and 2, and immunocompetent cell marker CD68 was measured in subcutaneous and visceral fat samples using real-time PCR. Adipose tissue was examined immunohistochemically for CD68-positive cells. Other biochemical parameters (insulin, glycated hemoglobin, cholesterol, LDL cholesterol, and triglycerides) were assessed in the two groups of patients at the same time. RESULTS: Serum concentrations of ADMA, C-reactive protein, pentosidine, interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly higher in obese CKD patients than in the control group; adiponectin was lower in the obese group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-alpha, CD68, adiponectin receptor-1, and monocyte chemoattractant protein-1 were significantly increased in the obese patients, whereas expression of adiponectin, interleukin-6, and adiponectin receptor-2 did not significantly differ between the patient groups. In general, mRNA expressions were higher in visceral than in subcutaneous samples (P < 0.01 vs. P < 0.05). Increased infiltration of subcutaneous and visceral adipose tissue by CD68-positive immunocompetent cells was found in the obese CKD group. With respect to lipid metabolism parameters, a small but significant increase in levels was found in the obese patients (P < 0.02). Changes in triglycerides were more marked in this group (P < 0.01) and a similar increase was noted in insulin and HbA1c levels (P < 0.02). CONCLUSION: Increased expression of proinflammatory cytokines and increased infiltration by immunocompetent cells were found in adipose tissue of obese patients with CKD stages 3-4. This upregulated inflammation may contribute to the induction of a systemic proinflammatory state in patients with CKD and could accelerate the progression of renal dysfunction.
- MeSH
- chronická renální insuficience komplikace metabolismus MeSH
- cytokiny metabolismus MeSH
- imunologické faktory metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita komplikace metabolismus MeSH
- tkáňová distribuce MeSH
- tuková tkáň metabolismus MeSH
- zánět komplikace metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- imunologické faktory MeSH