The implication of adipocyte ATP-binding cassette A1 and G1 transporters in metabolic complications of obesity.

Obesity is characterised by imbalance in lipid metabolism manifested by high concentrations of circulating triacylglycerols and total cholesterol as well as low high-density lipoprotein (HDL) levels. Abnormalities related to these lipids lead to metabolic complications such as type 2 diabetes, arterial hypertension and cardiovascular disease. Despite extensive research, it is still unclear why a subset of obese subjects develop metabolic syndrome, while others do not. The aim of our work was to assess total and plasma membrane expressions of cholesterol transport proteins: adipocyte ATP-binding cassette A1 (ABCA1), adipocyte ATP-binding cassette G1 (ABCG1), class B scavenger receptor (SR-BI) in visceral and subcutaneous adipose tissue of obese subjects with and without metabolic syndrome. To keep our preliminary study group uniform, we focused on women, who constitute the majority of bariatric patients. The study was performed on 34 patients: 24 morbidly obese women subjected to bariatric surgery, half of whom had metabolic syndrome; and 10 lean subjects undergoing elective laparoscopic cholecystectomy. Total and plasma membrane expressions of cholesterol transport proteins (SR-BI, ABCA1 and ABCG1) were assessed in samples of both visceral and subcutaneous adipose and analysed in relation to other clinical and laboratory parameters. We demonstrated lower plasma membrane expressions of ABCG1 in visceral adipose tissue of obese patients with metabolic syndrome as compared to lean ones. In addition, total ABCG1 expressions in both types of adipose tissue were lower in morbidly obese patients with metabolic syndrome compared to those without metabolic syndrome. Plasma membrane ABCA1 expressions in visceral adipose tissue were lower in the group of morbidly obese patients without metabolic syndrome, compared to lean patients. We did not find any significant differences in SR-BI expressions. Because of ABCG1 is responsible for cholesterol efflux to HDL, reduced plasma membrane expression of ABCG1 in VAT of morbidly obese women with metabolic syndrome may leads to a significantly decreased concentration of HDL in serum. This may be also confirmed by high positive correlation between both parameters.

Interleukin-6 deficiency modifies the effect of high fat diet on myocardial expression of fatty acid transporters and myocardial lipids.

Chronic inflammation is a critical feature of obesity in the development of myocardial dysfunction. The observations that interleukin-6 (IL-6) is implicated in lipid and glucose homeostasis as well as its connection with the pathogenesis of insulin resistance might suggest the involvement of this cytokine in metabolic disorders of the failing heart. In the present study we aimed to assess the effects of IL-6 ablation in mice fed with normal and high fat diet on the myocardial expression of glucose and fatty acid transporting proteins, and to evaluate the paralleled alterations in lipid content. We demonstrated that mice devoid of IL-6 exert reduced glucose transporter type 4 (GLUT-4) expression (-26%) and plasma membrane abundance (-43%), with no effect on glucose transporter type 1 (GLUT-1) content. Although there were no significant alterations in fatty acid translocase (FAT/CD36) and plasma membrane-associated fatty acid-binding protein (FABPpm) levels, we revealed a substantial decline in intramyocardial triacylglycerol level (-49%). Challenging of IL-6 knockout (KO) mice with high fat diet evoked an increase in FAT/CD36 expression (+19%) concomitantly with a trend for its reduced amount in plasma and mitochondrial membranes. Additionally, an increase in triacylglycerol level (+56%) was noticed, simultaneously with elevated content of saturated (+62%), monounsaturated (+69%) and polyunsaturated (+38%) fatty acids in this lipid fraction. The presented data reflect different roles of IL-6 in cardiomyocytes under selected conditions (i.e., normal and excessive lipid supply).

Effect of psoriasis activity and topical treatment on plasma epidermal growth factor (EGF) and its soluble receptor (sEGFR).

BACKGROUND: Pathogenesis of psoriasis involves epidermal growth factor (EGF) that participates in keratinocyte proliferation, angiogenesis and cell differentiation through binding to soluble epidermal growth factor receptor (sEGFR). It is synthesised by, among others, keratinocytes, especially within psoriatic skin. OBJECTIVE: To evaluate EGF and sEGFR plasma concentrations during topical psoriatic treatment. METHODS: Blood samples were collected from 51 patients with plaque psoriasis. EGF and sEGFR plasma concentrations were examined with immunoenzymatic method prior and 14 days after topical treatment. The outcomes were analyzed with respect to PASI. RESULTS: Mean EGF concentration was higher in the plasma of psoriatic patients compared to the control group (p = .401) while mean sEGFR concentration was over twofold lower compared to the control group (p < .001). After the therapy, an insignificant decrease in EGF plasma concentration (p = .835) and a significant increase in sEGFR concentration (p = .017) compared to initial values were observed. The coefficient of EGF/sEGFR concentration calculated for each individual had similar values before and after the treatment (p = .009), both of which were significantly higher compared to control group (respectively p < .001, p < .008). CONCLUSION: Epidermal growth factor and its soluble receptor may be a useful markers in monitoring clinical course of psoriasis and the effectiveness of therapy.

Influence of narrowband ultraviolet B phototherapy on serum tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in patients with psoriasis.

Psoriasis is characterized by keratinocyte resistance to apoptosis. We recently demonstrated an increase in serum tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in patients after topical treatment for psoriasis. We decided to verify whether narrowband ultraviolet B (NB-UVB) has a similar effect. Serum concentration of TWEAK was estimated in patients with exacerbated plaque psoriasis treated with NB-UVB. Baseline TWEAK levels were similar in patients with psoriasis and healthy controls, and Psoriasis Area and Severity Index (PASI) correlated inversely with TWEAK levels. Treatment with NB-UVB caused a significant reduction in PASI and concurrent increase in serum TWEAK. This finding may be due to increased expression of TWEAK receptor in psoriatic skin, which has been reported previously, with consequent binding of excess soluble TWEAK during treatment and subsequent release after treatment. Severity of plaque psoriasis and its improvement after NB-UVB treatment may be associated with TWEAK concentrations. The importance of our findings remains to be established.

Serum Fatty Acid-Binding Protein 4 is Increased in Patients with Psoriasis.

Psoriasis is associated with metabolic syndrome and cardiovascular disease. Fatty acid-binding proteins (FABP) have been recognized as predictors of these systemic disorders. The aim of this study was to assess correlations between levels of serum heart and adipocyte fatty acid-binding proteins (FABP3, FABP4) and disease severity, indicators of inflammation or metabolic disturbances, and topical treatment in psoriatic patients. Thirty-seven patients with relapse of plaque-type psoriasis and 16 healthy volunteers were recruited. Blood samples were collected before and after 14 days of therapy. Serum FABP concentrations were examined by enzyme-linked immunosorbent assay for correlation with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory or metabolic parameters, and treatment used. The median FABP4 serum levels were significantly increased (p = 0.038) in psoriatic patients, while FABP3 levels did not differ (p = 0.47) compared to the controls. No significant correlations were noted between the proteins and PASI, C-reactive protein (CRP), BMI, or levels of glucose or lipids. FABP3 significantly correlated with white blood count (p = 0.03) and aspartate aminotransferase (p = 0.04). After topical treatment, there was no significant change in serum FABP3 [11.5 (4.9-30.3) vs. 12.9 (3.5-30.3) ng/ml] (p = 0.96), whereas FABP4 was decreased [27,286 (20,344-32,257) vs. 23,034 (18,320-29,874) pg/ml] (p = 0.12), losing its basal significance. FABP4 may be a marker of psoriasis, and FABP3 may be associated with inflammation or liver disorders in psoriatic patients. FABP do not appear to be useful for determining disease severity or the effectiveness of antipsoriatic treatment.

Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels.

OBJECTIVE: Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients. METHODS: Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment. RESULTS: Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement. CONCLUSIONS: Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

Creatinine or cystatin C - which is a better index of renal function in morbid obesity?

PURPOSE: The most important index of renal function is estimated glomerular filtration rate (eGFR) which can be calculated from creatinine or cystatin C concentration in serum. There is uncertainty, which formula is best suited to assess renal function in morbidly obese patients. The aim of this study was to evaluate eGFR in patients with morbid obesity using formulas: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Grubb, Le Bricon, Hoek, Larsson, and to compare the obtained results. MATERIAL AND METHODS: In 40 morbidly obese patients, serum concentration of cystatin C and creatinine were assayed. Values of eGFR were calculated using the above-mentioned formulas. RESULTS: The mean value of eGFR ranged from 85.9 to 111.1 ml/min/1.73 m², depending on the formula. The biggest difference between the obtained values was 29% (Grubb vs. Hoek p<0.01). After calculation of eGFR from creatinine concentration (MDRD), 7 patients were qualified to the 2nd and 3rd stage of chronic renal disease, while application of Hoek's formula, based on cystatin C concentration, allotted 27 patients to 2nd and 3rd stage of chronic renal disease. Le Bricon formula gave eGFR values, that correlated best with albuminuria. CONCLUSION: eGFR calculated using Le Bricon formula based on the cystatin C concentration was significantly lower than eGFR calculated from creatinine concentration and was more closely associated with albuminuria. Relying only on creatinine concentration to estimate glomerular filtration rate can lead to underestimation of renal malfunction in obese patients.

Effect of psoriasis treatment on plasma concentrations of metalloproteinase-1 and tissue inhibitor of metalloproteinases-1.

AIM: The aim of this study was to evaluate the effect of psoriasis treatment on plasma concentrations of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with respect to disease severity. METHODS: MMP-1 and TIMP-1 were measured using an enzyme immunoassay in plasma of 32 patients before and after topical treatment. Data were analysed with respect to baseline values of the Psoriasis Area and Severity Index (PASI). RESULTS: Baseline plasma concentrations of both TIMP-1 and MMP-1 (1487 +/- 102 and 21.0 +/- 2.5 ng/mL, respectively) were significantly higher (P = 0.02 and 0.03, respectively) than normal. Both TIMP-1 and MMP-1 decreased significantly after completion of treatment to values similar to normal (1112 +/- 127 and 11.3 +/- 1.3 ng/mL, respectively). There was a significant positive correlation (r = 0.522) between baseline PASI and TIMP-1 values. Significant differences were observed between baseline TIMP-1 concentrations in groups with PASI < 15 and PASI > 20. Baseline values (1697 +/- 162 ng/mL) in patients with severe course of the disease (PASI > 20) were significantly elevated in comparison to normal values. Treatment caused a decrease in TIMP-1 plasma concentrations in all groups, but a significant difference was noted only in patients with pretreatment PASI > 20. Baseline MMP-1 concentrations exceeded significantly normal values only in patients with PASI < 15 (27.2 +/- 6.3 ng/mL) and 15-20 (18.4 +/- 1.4 ng/mL). Treatment caused a significant decrease in MMP-1-values in all groups to levels similar to normal. CONCLUSIONS: Our results confirm the role of TIMP-1 and MMP-1 in the pathogenesis of psoriasis. Pretreatment plasma TIMP-1 increased whereas MMP-1 decreased in patients with a more severe course of the disease. However, successful treatment causes normalization of these plasma protein concentrations irrespective of psoriasis baseline activity.