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).

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.