Antioxidant and antiradical activities depend on adrenal tumor type.

The aim of the study was to assess the total antioxidant/oxidant status in the plasma and urine of patients with adrenal tumors. The study group consisted of 60 patients (31 women and 29 men) with adrenal masses, classified into three subgroups: non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma. The number of patients was set a priori based on our previous experiment (α = 0.05, test power = 0.9). Antioxidant activity (Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Oxidative Stress Index (OSI)) and antiradical activity (Radical-Scavenging Activity Assay (DPPH), Ferric-Reducing Antioxidant Power (FRAP)) were measured using colorimetric methods. FRAP level was decreased in plasma and urine incidentaloma (p<0.0001), pheochromocytoma (p<0.0001) and Cushing's/Conn's adenoma (p<0.0001), while DPPH antiradical activity only in plasma of patients with adrenal masses (p<0.0001). Plasma TAC was increased in incidentaloma patients (p=0.0192), whereas in pheochromocytoma group (p=0.0343) was decreased. Plasma and urine TOS (p<0.0001) and OSI (p<0.01) were significantly higher in patients with adrenal tumors. In pheochromocytoma patients, plasma and urine TAC (p=0.001; p=0.002), as well as plasma plasma DPPH (p=0.007) and urine FRAP (p=0.017) correlated positively with normethanephrine. We are the first who showed reduced radical scavenging capacity in the plasma/urine of patients with adrenal masses. Nevertheless, plasma TAC was significantly higher in the incidentaloma group compared to controls. Therefore, plasma and urinary antioxidant and antiradical activities depend on the presence of the tumor. Lower levels of TAC, DPPH and FRAP clearly indicate a reduced ability to scavenge free radicals and thus a lack of effective protection against oxidative stress in patients with adrenal tumors. Both plasma and urine redox biomarkers can be used to assess systemic antioxidant status in adrenal tumor patients.

α-Lipoic Acid Reduces Ceramide Synthesis and Neuroinflammation in the Hypothalamus of Insulin-Resistant Rats, While in the Cerebral Cortex Diminishes the ß-Amyloid Accumulation.

Background: Oxidative stress underlies metabolic diseases and cognitive impairment; thus, the use of antioxidants may improve brain function in insulin-resistant conditions. We are the first to evaluate the effects of α-lipoic acid (ALA) on redox homeostasis, sphingolipid metabolism, neuroinflammation, apoptosis, and ß-amyloid accumulation in the cerebral cortex and hypothalamus of insulin-resistant rats. Methods: The experiment was conducted on male cmdb/outbred Wistar rats fed a high-fat diet (HFD) for 10 weeks with intragastric administration of ALA (30 mg/kg body weight) for 4 weeks. Pro-oxidant and pro-inflammatory enzymes, oxidative stress, sphingolipid metabolism, neuroinflammation, apoptosis, and ß-amyloid level were assessed in the hypothalamus and cerebral cortex using colorimetric, fluorimetric, ELISA, and HPLC methods. Statistical analysis was performed using three-way ANOVA followed by the Tukey HSD test. Results: ALA normalizes body weight, food intake, glycemia, insulinemia, and systemic insulin sensitivity in HFD-fed rats. ALA treatment reduces nicotinamide adenine dinucleotide phosphate (NADPH) and xanthine oxidase activity, increases ferric-reducing antioxidant power (FRAP) and thiol levels in the hypothalamus of insulin-resistant rats. In addition, it decreases myeloperoxidase, glucuronidase, and metalloproteinase-2 activity and pro-inflammatory cytokines (IL-1ß, IL-6) levels, while in the cerebral cortex ALA reduces ß-amyloid accumulation. In both brain structures, ALA diminishes ceramide synthesis and caspase-3 activity. ALA improves systemic oxidative status and reduces insulin-resistant rats' serum cytokines, chemokines, and growth factors. Conclusion: ALA normalizes lipid and carbohydrate metabolism in insulin-resistant rats. At the brain level, ALA primarily affects hypothalamic metabolism. ALA improves redox homeostasis by decreasing the activity of pro-oxidant enzymes, enhancing total antioxidant potential, and reducing protein and lipid oxidative damage in the hypothalamus of HFD-fed rats. ALA also reduces hypothalamic inflammation and metalloproteinases activity, and cortical ß-amyloid accumulation. In both brain structures, ALA diminishes ceramide synthesis and neuronal apoptosis. Although further study is needed, ALA may be a potential treatment for patients with cerebral complications of insulin resistance.

Cross-Talk Between Nitrosative Stress, Inflammation and Hypoxia-Inducible Factor in Patients with Adrenal Masses.

BACKGROUND: Adrenal masses are the most common of all human tumors. The role of nitrosative stress and inflammation in cancer development has already been demonstrated. However, it is not known whether they are involved in the pathogenesis of adrenal tumors. The aim of the study was to investigate a cross-talk between nitrosative stress, inflammation and hypoxia-inducible factor (HIF-1α) in 75 patients with different types of adrenal masses (non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma). METHODS: The plasma concentrations of total nitric oxide (NO), S-nitrosothiols, peroxynitrite nitrotyrosine and the activity of serum myeloperoxidase (MPO) were measured spectrophotometrically, whereas concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1 alpha (HIF-1α) were measured using commercial ELISA kits. The control group consisted of 50 healthy people matched by age and sex to the study group. The number of subjects was determined a priori based on our previous experiment (power of the test = 0.9; α = 0.05). RESULTS: We found significantly higher nitrosative stress (↑nitric oxide, ↑peroxynitrite, ↑S-nitrosothiols and ↑nitrotyrosine) in the plasma of patients with adrenal tumors, which was accompanied by increased inflammatory (↑myeloperoxidase, ↑interleukin 1 beta and ↑tumor necrosis factor α) and hypoxia (HIF-1α) biomarkers. Peroxynitrite and nitrotyrosine were positively correlated with aldosterone level. Nitrosative stress was also associated with inflammation and HIF-1α. Interestingly, plasma nitrotyrosine and serum MPO differentiated patients with adrenal tumor from healthy individuals with high sensitivity and specificity. Moreover, using multivariate regression analysis, we showed that ONOO- and IL-1ß depended on cortisol level, while ONOO-, nitrotyrosine and HIF-1α were associated with aldosterone. Unfortunately, none of the assessed biomarkers differentiated between tumor types studied, suggesting that the severity of nitrosative damage and inflammation are similar in patients with incidentaloma, pheochromocytoma, and Cushing's or Conn's adenoma. CONCLUSION: Adrenal tumors are associated with increased protein nitration/S-nitrosylation and inflammation.

Effects of age and gender on the redox homeostasis of morbidly obese people.

Obesity is a chronic disease of complex etiology. Recent evidence suggests that obesity is caused by inflammation of adipose tissue leading to metabolic disorders, cardiovascular disease and cancer. This is the first study to evaluated the effects of age and gender on redox homeostasis, glutathione metabolism, and oxidative damage to plasma/serum lipids and proteins in morbidly obese patients. The study included 120 (60 men and 60 women) morbidly obese patients with class 3 obesity (BMI > 40 kg/m2), classified into three groups depending on age: 20-39 years (n = 20), 40-59 years (n = 20) and 60 years or older (n = 20). The number of patients was calculated a priori based on our previous experiment. We observed a reduction in serum activity of antioxidant enzymes (↓SOD) and plasma concentration of non-enzymatic antioxidants (↓GSH) in obese patients compared to the lean controls, which further decreased with age. Redox status (↑TAC, ↑TOS and ↓OSI) in morbidly obese men and women was shifted towards oxidation. Moreover, lipid (↑MDA and ↑LOOH) and protein (↑AOPP, ↑AGE and ↑Amadori products) damage products of oxidation and nitrosylation/nitration (↑total NO, ↑S-nitrosothiols, ↑peroxynitrite and ↑nitrotyrosine) were elevated in both genders of morbidly obese patients and were higher in the elderly. Interestingly, the concentrations of oxidative and nitrosative stress markers were generally higher in obese men compared to obese women at the same age. Summarizing, we showed that the total antioxidant/oxidant potential of obese patients is significantly increased and shifted towards oxidation. Obese patients have increased lipid and protein oxidation, glycation and nitration as compared to the lean controls. Disturbances in redox homeostasis increase with age in obese patients. Oxidative and nitrosative stress are more intense in men than in women at the same age.

Does TBC1D4 (AS160) or TBC1D1 Deficiency Affect the Expression of Fatty Acid Handling Proteins in the Adipocytes Differentiated from Human Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Obtained from Subcutaneous and Visceral Fat Depots?

TBC1D4 (AS160) and TBC1D1 are Rab GTPase-activating proteins that play a key role in the regulation of glucose and possibly the transport of long chain fatty acids (LCFAs) into muscle and fat cells. Knockdown (KD) of TBC1D4 increased CD36/SR-B2 and FABPpm protein expressions in L6 myotubes, whereas in murine cardiomyocytes, TBC1D4 deficiency led to a redistribution of CD36/SR-B2 to the sarcolemma. In our study, we investigated the previously unexplored role of both Rab-GAPs in LCFAs uptake in human adipocytes differentiated from the ADMSCs of subcutaneous and visceral adipose tissue origin. To this end we performed a single- and double-knockdown of the proteins (TBC1D1 and TBC1D4). Herein, we provide evidence that AS160 mediates fatty acid entry into the adipocytes derived from ADMSCs. TBC1D4 KD resulted in quite a few alterations to the cellular phenotype, the most obvious of which was the shift of the CD36/SR-B2 transport protein to the plasma membrane. The above translated into an increased uptake of saturated long-chain fatty acid. Interestingly, we observed a tissue-specific pattern, with more pronounced changes present in the adipocytes derived from subADMSCs. Altogether, our data show that in human adipocytes, TBC1D4, but not TBC1D1, deficiency increases LCFAs transport via CD36/SR-B2 translocation.

Antioxidant Barrier and Oxidative Damage to Proteins, Lipids, and DNA/RNA in Adrenal Tumor Patients.

This study is the first to assess redox balance, glutathione metabolism, and oxidative damage to RNA/DNA, proteins, and lipids in the plasma/serum and urine of patients with adrenal masses. The study included 70 patients with adrenal tumors divided into three subgroups: incidentaloma (n = 30), pheochromocytoma (n = 20), and Cushing's/Conn's adenoma (n = 20), as well as 60 healthy controls. Blood and urine samples were collected before elective endoscopic adrenalectomy. Antioxidant defense capacity was significantly decreased (serum/plasma: superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), uric acid (UA); urine: SOD, GSH, UA) in patients with adrenal masses. The oxidative damage to proteins (advanced glycation end products (AGE), advanced oxidation protein products (AOPP)) and lipids (lipid hydroperoxides (LOOH), and malondialdehyde (MDA)) was higher in the plasma and urine of these patients. Plasma MDA and DNA/RNA oxidation products, with high sensitivity and specificity, can help to diagnose pheochromocytoma. This biomarker differentiates patients with pheochromocytoma from Cushing's/Conn's adenoma as well as from heathy controls. Plasma RNA/DNA oxidation was also positively correlated with urine metanephrine. Oxidative stress can play a crucial role in adrenal tumors. However, further studies are required to clarify the role of redox signaling in adrenal masses.

The influence of patient's age on metabolic and bariatric results of laparoscopic sleeve gastrectomy in 2-year observation.

BACKGROUND: The incidence of obesity has been constantly growing and bariatric procedures are considered to be the most effective treatment solution for morbidly obese patients. The results of laparoscopic sleeve gastrectomy (LSG) may differ depending on patient's age, gender, preoperative body mass index (BMI) and physical activity. METHODS: The aim of this study was to evaluate age-related differences in the outcome of LSG in terms of weight loss parameters, lipid and carbohydrate profile. The retrospective analysis of 555 patients who had undergone LSG was performed to compare the metabolic outcomes of surgery in individuals < 45 and ≥ 45 years old. Evaluation of weight loss parameters along with selected laboratory data was performed to demonstrate the results of LSG in 2 years follow-up. RESULTS: Overall, 238 males and 317 females (43%/57%) with median age of 43 years and median preoperative BMI of 46.41 (42.06-51.02) kg/m2 were analyzed. Patients in both groups presented significant weight loss at 24 months after the surgery with comparable percentage of total weight loss (40.95% in < 45 years old group and 40.44% in ≥ 45 years old group). The percentage of excess weight loss (78.52% vs. 74.53%) and percentage of excess BMI loss (91.95% vs. 88.01%) were higher in patients < 45 years old. However, the differences were not statistically significant (p = 0.662, p = 0.788 respectively). Patients under 45 years old experienced faster decrease in fasting glucose level that was observed after only 3 months (109 mg/dl to 95 mg/dl in < 45 years old group vs. 103.5 mg/dl to 99.5 mg/dl in ≥ 45 years old group, p < 0.001). Both groups presented improvement of lipid parameters during the observation. However, patients < 45 years old achieved lower values of LDL at 3 and 12 months follow-up (115 mg/dl vs. 126 mg/dl, p = 0.010; 114.8 mg/dl vs. 122 mg/dl, p = 0.002). Younger group of patients also showed superior improvement of triglycerides level. CONCLUSIONS: LSG results in significant weight loss in all patients regardless age. In turn, superior and faster improvement in lipid and carbohydrate profile is achieved in patients under 45 years old.

Bariatric Surgery Normalizes Protein Glycoxidation and Nitrosative Stress in Morbidly Obese Patients.

The results of recent studies indicate the key role of nitrosative stress and protein oxidative damage in the development of morbid obesity. Nevertheless, the effect of bariatric surgery on protein oxidation/glycation and nitrosative/nitrative stress is not yet known. This is the first study evaluating protein glycoxidation and protein nitrosative damage in morbidly obese patients before and after (one, three, six and twelve months) laparoscopic sleeve gastrectomy. The study included 50 women with morbid obesity as well as 50 age- and gender-matched healthy controls. We demonstrated significant increases in serum myeloperoxidase, plasma glycooxidative products (dityrosine, kynurenine, N-formyl-kynurenine, amyloid, Amadori products, glycophore), protein oxidative damage (ischemia modified albumin) and nitrosative/nitrative stress (nitric oxide, peroxy-nitrite, S-nitrosothiols and nitro-tyrosine) in morbidly obese subjects as compared to lean controls, whereas plasma tryptophan and total thiols were statistically decreased. Bariatric surgery generally reduces the abnormalities in the glycoxidation of proteins and nitrosative/nitrative stress. Noteworthily, in the patients with metabolic syndrome (MS+), we showed no differences in most redox biomarkers, as compared to morbidly obese patients without MS (MS-). However, two markers: were able to differentiate MS+ and MS- with high specificity and sensitivity: peroxy-nitrite (>70%) and S-nitrosothiols (>60%). Further studies are required to confirm the diagnostic usefulness of such biomarkers.

The Impact of Hypertension and Metabolic Syndrome on Nitrosative Stress and Glutathione Metabolism in Patients with Morbid Obesity.

In this pathbreaking study, we evaluated nitrosative stress in morbidly obese patients with and without metabolic syndrome. 62 women with class 3 obesity (BMI > 40 kg/m2) were divided into three subgroups: obese patients (OB), obese patients with hypertension (OB+HYP), and obese patients with metabolic syndrome (OB+MS). In comparison to the lean patients, OB had increased levels of serum myeloperoxidase (MPO), plasma nitric oxide (NO), S-nitrosothiols, and peroxynitrite (ONOO-), as well as nitrotyrosine, while oxidized glutathione (GSSG) rose only in OB+HYP group. Interestingly, ONOO- was significantly higher in OB+HYP and OB+MS as compared to OB group, while MPO only in OB+MS group. OB+MS had greater nitrotyrosine and S-nitrosothiol values than OB+HYP. Moreover, peroxynitrite could differentiate OB from OB+HYP and OB+MS (AUC 0.9292; p < 0.0001; 87.5% sensitivity, 90% specificity) as well as between OB and OB+MS group (AUC 0.9125; p < 0.0001; 81.25% sensitivity, 83.33%). In conclusion, we showed that MPO activity, NO formation, and nitrosative damage to proteins parallel the progression of metabolic disturbances of obesity. Evaluation of ONOO- concentrations may help predict the development of hypertension and metabolic syndrome in patients with morbid obesity; however, longer-term studies are required for larger numbers of patients.

Markers of metastatic colorectal cancer.

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death. However, early diagnosis of CRC metastases offers a chance of long-term survival in as much as 40% of patients after curative treatment. Current guidelines are based on clinical examination, carcinoembryonic antigen (CEA) testing, computed tomography scanning, and endoscopic surveillance. Although CEA is the most widely used laboratory test, it has very low sensitivity (30-40%). Moreover, there is no evidence to support the association of CEA testing with improved survival or quality of life. Thus, novel markers with greater specificity and sensitivity are needed. The aim of this review was to define the role of available laboratory markers in early diagnosis of metastatic CRC. We identified novel tests with the highest association to metastatic CRC: circulating tumour DNA, growth/differentiation factor 15, and ß6-integrin. We also discuss other promising markers, although most of the studies are preliminary and require validation.

Impact of Weight Loss on the Total Antioxidant/Oxidant Potential in Patients with Morbid Obesity-A Longitudinal Study.

The assessment of total antioxidant activity seems to have a higher diagnostic value than the evaluation of individual antioxidants separately. Therefore, this is the first study to assess the total antioxidant/oxidant status in morbidly obese patients undergoing bariatric surgery. The study involved 60 patients with Class 3 obesity (BMI > 40 kg/m2) divided into two equal subgroups: morbidly obese patients without and with metabolic syndrome. The analyses were performed in plasma samples collected before surgery as well as 1, 3, 6, and 12 months after a laparoscopic sleeve gastrectomy. Total antioxidant capacity (TAC), ferric-reducing antioxidant power (FRAP), DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical assay, and total oxidant status (TOS) were significantly higher before surgery (as compared to the healthy controls, n = 60) and generally decreased after bariatric treatment. Interestingly, all assessed biomarkers correlated positively with uric acid content. However, the total antioxidant/oxidant potential did not differ between obese patients without metabolic syndrome and those with both obesity and metabolic syndrome. Only DPPH differentiated the two subgroups (p < 0.0001; AUC 0.8) with 73% sensitivity and 77% specificity. Plasma TAC correlated positively with body mass index, waist-hip ratio, serum insulin, and uric acid. Therefore, TAC seems to be the best biomarker to assess the antioxidant status of obese patients.

A Longitudinal Study of the Antioxidant Barrier and Oxidative Stress in Morbidly Obese Patients after Bariatric Surgery. Does the Metabolic Syndrome Affect the Redox Homeostasis of Obese People?

This is the first study to evaluate both the antioxidant barrier, glutathione metabolism, and oxidative damage to proteins and lipids in morbidly obese patients undergoing bariatric treatment. The study included 65 patients with class 3 obesity divided into two subgroups: morbidly obese patients without metabolic syndrome (OB) and obese patients with metabolic syndrome (OB + MS). Blood samples were collected before surgery as well as one, three, six, and twelve months after the bariatric treatment. Superoxide dismutase and reduced glutathione (GSH) were significantly decreased, whereas glutathione reductase and uric acid were enhanced in morbidly obese patients before bariatric surgery as compared to lean control. Moreover, in the OB group, we observed the increase of superoxide dismutase (SOD) and the decrease of uric acid (UA) after the bariatric treatment; however, these changes were not observed in the OB + MS group. The oxidative damage to proteins (advanced glycation end products, AGE; advanced oxidation protein products, AOPP) and lipids (8-isoprostanes, 8-isop; 4-hydroxynoneal) was higher in OB as well as OB + MS patients. We noticed that AGE and AOPP levels diminished after the bariatric treatment, whereas redox status (ratio of GSH to oxidized glutathione) was still reduced in the OB + MS group. Summarizing, morbid obesity is associated with disturbances in the antioxidant barrier and enhanced oxidative damage to proteins and lipids. Although bariatric surgery improves redox homeostasis in obese patients, those with metabolic syndrome show a continuous decrease in the antioxidant status. In patients undergoing bariatric treatment, antioxidant supplementation may be considered.

The impact of laparoscopic adrenalectomy on renal function. Results of a prospective randomised clinical trial.

INTRODUCTION: Laparoscopic adrenalectomy is the gold standard management of benign adrenal masses and isolated metastases to adrenal glands. Two techniques of endoscopic adrenalectomy: lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) seem to be equally safe and effective. Recent studies suggest advantages of PRA over LTA in terms of lower intensity of postoperative pain, shorter hospital stay, faster recovery, and lower early morbidity. However, PRA involves high insufflation pressure of CO2 within a limited retroperitoneal space. The aim of our study was to prospectively assess the effect of LTA versus PRA laparoscopic adrenalectomies on renal function. MATERIAL AND METHODS: We randomly assigned patients referred for unilateral adrenalectomy to either LTA (n = 33) or PRA (n = 44). The inclusion criteria were: hormonal activity and/or tumour diameter > 4 cm and/or suspicion of metastasis to adrenal gland. The exclusion criteria comprised: tumours > 8 cm, results of imaging studies suggesting primary invasive malignancy, and refusal to undergo randomisation. The patients were prospectively followed for a minimum of six months. Serum creatinine, cystatin C, and urinary neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively and at postoperative days: 1, 7, and 30. RESULTS: We found increased concentrations of urinary NGAL at day 1 following laparoscopic adrenalectomy using PRA, as compared to LTA. Patients undergoing right-sided PRA had increased creatinine concentrations, as compared to left-sided PRA. Patients with aldosterone-producing adenoma had decreased preoperative eGFR as compared to subjects with non-functioning incidentaloma. NGAL increased significantly in this group postoperatively. All the disturbances normalised within one month postoperatively. CONCLUSIONS: Renal function impairment after PRA may result from compression of inferior vena cava by high retroperitoneal pressure during right-sided adrenalectomy. Despite the transient character of the observed abnormalities, we suggest that patients with high risk of acute kidney injury may benefit from an alternative technique of adrenalectomy using LTA.

Laparoscopic adrenalectomy: lateral transperitoneal versus posterior retroperitoneal approach - prospective randomized trial.

INTRODUCTION: Laparoscopic adrenalectomy has become the gold standard of surgical treatment for benign adrenal masses. Two alternative surgical approaches are currently advocated: the lateral transperitoneal approach (LTA) and the posterior retroperitoneal approach (PRA). Several randomized trials have compared LTA to PRA, but most of them included small numbers of patients or had stringent inclusion criteria. AIM: To compare clinical results of LTA and PRA endoscopic adrenalectomies for tumors < 8 cm with wide inclusion criteria. MATERIAL AND METHODS: We randomized 77 patients to either LTA (n = 33) or PRA (n = 44). The groups were comparable in terms of age, gender proportions, body mass index, tumor size, clinical and pathological diagnosis. We analyzed duration of surgery, intraoperative blood loss, postoperative pain, length of hospital stay and postoperative morbidity. RESULTS: The follow-up concerned 98.8% of patients and was on average 28 (8-47) months long. There were no conversions. We identified significantly lower intensity of pain assessed 24 h after surgery in the PRA group (3.4 ±1), as compared to LTA (4.2 ±1), with lower prevalence of shoulder pain (2.3% vs. 30.3%, respectively). Postoperative hospital stay was shorter in the PRA (1.14 ±0.4) than in the LTA (1.36 ±0.5) group. Perioperative morbidity concerned 4 patients in each group with pain requiring oral analgesia > 7 days. CONCLUSIONS: To our knowledge this is the largest prospective randomized study comparing LTA to PRA. We demonstrated safety, efficacy and very low morbidity of both techniques. The PRA proved superior to LTA in terms of lower intensity of postoperative pain and shorter hospital stay.

Metabolic Syndrome is Associated with Ceramide Accumulation in Visceral Adipose Tissue of Women with Morbid Obesity.

OBJECTIVE: Accelerated transmembrane transport of long-chain fatty acids dependent on fatty acid transporters is responsible for lipid accumulation and, eventually, the development of metabolic syndrome. This study determined the content of lipids (ceramide [CER], diacylglycerol [DAG], triacylglycerol, and free fatty acid [FFA]) and the expression of fatty acid translocase (FAT/CD36) and plasma membrane fatty acid-binding protein in visceral adipose tissue (VAT) and subcutaneous adipose tissue of women with morbid obesity without metabolic syndrome (MetSx-) or with metabolic syndrome (MetSx+) and compared the results with those of lean controls without metabolic syndrome. METHODS: Lipid content and fatty acid composition in each lipid subclass were estimated by gas liquid chromatography. For total, plasma membrane, and mitochondrial expression of fatty acid transporters, subfractionation with subsequent Western blot technique was used. RESULTS: A greater content of triacylglycerol in VAT of participants with obesity (MetSx-) was found. However, only the MetSx+ subjects had increased content of CER in VAT in relation to subcutaneous adipose tissue in MetSx+ and lean individuals. This was accompanied by increased total and membrane expression of FAT/CD36 in VAT in MetSx+ subjects. Accordingly, mitochondrial expression of FAT/CD36 and plasma membrane fatty acid-binding protein was decreased in both groups of subjects with obesity. CONCLUSIONS: Metabolic syndrome is associated with the accumulation of CER in VAT, possibly related to increased FAT/CD36 protein expression.

Lack of pronounced changes in the expression of fatty acid handling proteins in adipose tissue and plasma of morbidly obese humans.

BACKGROUND/OBJECTIVES: Fatty acid handling proteins are involved in the process of accumulation of lipids in different fat tissue depots. Thus, the aim of the study was to estimate the expression of both fatty acid transport and binding proteins in the subcutaneous (SAT) and visceral adipose tissue (VAT) of patients with morbid obesity without metabolic syndrome, as well as the plasma concentrations of these transporters. SUBJECTS/METHODS: Protein (Western blotting) and mRNA (Real-time PCR) expression of selected fatty acid handling proteins was assessed in the visceral and subcutaneous adipose tissue of 30 patients with morbid obesity. The control group consisted of 10 lean age-matched patients. Plasma levels of fatty acid protein transporters were also evaluated using ELISA method. Moreover, total plasma fatty acid composition and concentration was determined by gas-liquid chromatography (GLC). RESULTS: Significant increase in fatty acid translocase (FAT/CD36) mRNA (P = 0.03) and plasmalemmal (P = 0.01) expression was observed in VAT of patients with morbid obesity vs. lean subjects together with elevation of lipoprotein lipase (LPL), as well as peroxisome proliferator-activated receptor γ (PPARγ) in both examined compartments of adipose tissue. Moreover, in obese subjects plasma concentration of RBP4 was markedly elevated (P = 0.04) and sCD36 level presented a tendency for an increase (P = 0.08) with concomitant lack of changes in FABP4 concentration (P > 0.05). CONCLUSIONS: Fatty acid transport into adipocytes may be, at least in part, related to the increased expression of FAT/CD36 in the VAT of morbidly obese patients, which is accompanied by augmented expression of LPL, as well as PPARγ. Probably, alternations in plasma concentrations of RBP4 and sCD36 in obese patients are associated with "unhealthy" fat distribution.

The role of CD36 receptor in the pathogenesis of atherosclerosis.

Atherosclerosis is a progressive, chronic inflammation in artery walls. Oxidized low density lipoproteins (ox-LDL) play an important role in atherosclerotic plaque formation. ox-LDL are taken up by macrophages mainly through scavenger receptors, among which CD36 is considered to be the most important. Animal studies have shown that crossing atherogenic mice with a strain lacking the expression of CD36 prevented the development of atherosclerosis despite a diet rich in saturated LCFA. In humans, autopsy studies performed in obese patients have demonstrated increased expression of CD36 receptor on macrophages, comprised within atherosclerotic plaques. Until recently it had been believed that CD36 is a major player in atherosclerosis progression in humans. However, recent studies challenge this conviction, showing increased incidence of coronary heart disease in the subgroup of patients with decreased expression of CD36. This article reviews the role of CD36 receptor in the development of atherosclerosis. The authors also discuss current possibilities to interfere with CD36, their potential benefits and hazards.

Increase in circulating sphingosine-1-phosphate and decrease in ceramide levels in psoriatic patients.

Psoriasis is characterized by hyperproliferation, deregulated differentiation and impaired apoptosis of keratinocytes. Mechanisms of lipid profile disturbances and metabolic syndrome in the psoriatic patients are still not fully understood. Sphingolipids, namely ceramides (CER) and sphingosine-1-phosphate (S1P) are signal molecules which can regulate cell growth, apoptosis and immune reactions. The aim of the study was to evaluate circulating CER and S1P levels in plaque-type psoriasis and their associations with the disease activity, inflammatory or metabolic markers and the presence of psoriatic comorbidities. Eighty-five patients with exacerbated plaque-type psoriasis and thirty-two healthy controls were enrolled. Serum CER and S1P concentrations before the treatment were examined. General patient characteristics included: PASI (Psoriasis Area and Severity Index), BMI (Body Mass Index), inflammatory and biochemical markers, lipid profile and presence of psoriatic comorbidities. Total serum concentration of CER was significantly decreased (p = 0.02) and concomitantly S1P levels significantly increased (p = 0.002) in psoriatic patients compared to the healthy control group. Among patients with psoriasis no significant correlations with the disease activity and inflammation markers were observed and only patients with psoriatic arthritis had significantly higher CER total concentration. Serum sphingolipid disturbances in psoriatic patients were observed. Decreased total CER and increased S1P serum levels may reflect their epidermal altered composition and metabolism. Patients with psoriatic arthritis have higher CER levels than psoriasis with skin involvement only. It might provide additional predictive value for psoriatic arthritis and may convey higher risk of metabolic and cardiovascular disease development in this group of patients.

Saliva of obese patients - is it different?

Obesity is a major public health concern that increases the risk of cardiovascular disease, type 2 diabetes and cancer. The incidence of obesity has increased significantly in recent years, not only in adults, but also in adolescents and children. This is evidenced by rapidly developing bariatric surgery, the most effective method of treating morbid obesity. Obesity is a multifactorial disease, and its pathogenesis is not completely understood. Numerous studies have been performed to clarify pathogenetic mechanisms, based mostly on blood and sometimes urine samples. Saliva is easily accessible and can be obtained non-invasively. Our aim was to review studies performed on saliva obtained from obese subjects in order to answer the title question. Obese people have different composition of salivary bacteria. Changes in the concentration of sialic acid, phosphorus and peroxidase activity as well as a lower flow rate of stimulated whole saliva promote dental caries and periodontal disease. Concentrations of salivary uric acid, endocannabinoids and CRP are increased in obesity and may provide a useful index of cardiometabolic risk. Assessment of fasting salivary ghrelin might facilitate choosing the best type of bariatric surgery for a specific patient. A significant decrease in salivary cortisol in women with morbid obesity also seems interesting. There is sufficient evidence to state that the saliva of obese and lean subjects is different. Saliva as an easily accessible research material seems promising, as shown by the few studies performed so far.

The diagnostics of colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent human malignant neoplasms. CRC has an estimated incidence of more than 1,000,000 new cases annually worldwide. Approximately one out of three people who develop CRC dies from the disease. Furthermore, CRC often affects inhabitants of industrialized countries in comparison to less developed countries. Several markers of colon cancer, including CEA, CA-19-9, TPS, TAG-72 and lysosomal hydrolases, have been identified and are now being adopted in routine clinical practice. Increased values of these markers are often the first signal of recurrence or metastases, which is useful in prediction and prognosis of clinical outcome of patients with CRC. Determination of the activity of lysosomal exoglycosidases in body fluids may bring some hope of improving diagnosis of colorectal cancer. However, it has to be remembered that currently the most effective diagnostic method of CRC is endoscopy.