Mariusz Wylezol

Bio: Mariusz Wylezol is an academic researcher from Medical University of Silesia. The author has contributed to research in topics: Medicine & Obesity. The author has an hindex of 10, co-authored 18 publications receiving 390 citations.

Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome.

Abstract: Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely related to fasting and postprandial alterations of concentrations of PYY(3-36), CCK and ghrelin, suggesting that determination of gut hormones controlling food intake might be considered as a valuable tool to assess the progression of MS to comorbidities of obesity.

Liver visfatin expression in morbidly obese patients with nonalcoholic fatty liver disease undergoing bariatric surgery.

Abstract: BACKGROUND Visfatin has been identified as a new adipokine with proinflammatory and immunomodulating properties. It seems to interfere with immune and fibrogenic process in nonalcoholic fatty liver disease (NAFLD). The aim was to assess visfatin expression in the liver tissue and its association with biochemical parameters and morphological features in NAFLD patients. MATERIAL AND METHODS The study included 40 severely obese patients with NAFLD who underwent intraoperative wedge liver biopsy during a bariatric operation. Immunohistochemical assay was carried out with the use of a visfatin mice monoclonal antibody. RESULTS Visfatin expression in the liver was observed in all patients. The expression was significantly higher in patients with fibrosis (p = 0.036) and was positively correlated with the fibrosis stage (r = 0.52, p = 0.03). There was no difference between patient with nonalcoholic steatohepatitis (NASH) and simple steatosis (p = 0.54). Inflammatory activity and NAS (NAFLD Activity Score) score were not associated with visfatin expression. There was a tendency of more evident visfatin liver expression in morbidly obese patients with diabetes mellitus. CONCLUSION Our study showed a positive association between visfatin and the fibrosis stage in NAFLD. This observation suggests a potential role of this adipokine in the pathogenesis and progression of NAFLD. Visfatin expression does not seem to be associated with liver steatosis and inflammation.

Breast cancer progression and expression of blood group-related tumor-associated antigens.

Abstract: There is sufficient evidence that blood group related Lewis antigens are tumor-associated molecules. We have conducted immunohistochemical analysis of the expression of Lewis antigens in breast cancer tissue as an indicator of the degree of malignancy and as a prognostic factor. The studies were performed by examining 43 female patients diagnosed with invasive ductal carcinoma of the breast. Postoperative specimens were stained immunohistochemically using a panel of monoclonal antibodies (MAbs) specific for tumor-associated antigens: sialosyl LewisA, LewisA, LewisB, LewisX, and LewisY. The aims of the study were to compare the appearance of metastases, degree of cancer stage (pTNM), and its histologic differentiation with the expression of Lewis phenotype. The evaluation of antigen expression was performed quantitatively and independently by two pathologists. Statistical significance was defined by Mann–Whitney test. The presented analysis of Lewis antigens showed higher expression of LeB and LeA (p = 0.0...

Hepatic angiogenesis and fibrosis are common features in morbidly obese patients

Abstract: Background A mass of visceral adipose tissue is one of the most important determinants of progressive liver injury in nonalcoholic fatty liver disease (NAFLD). In accordance, nonalcoholic steatohepatitis (NASH) and fibrosis are believed to occur more commonly in morbidly obese patients compared with nonobese NAFLD patients.

Red Blood Cell Aggregation and Deformability among Patients Qualified for Bariatric Surgery

Abstract: The study presents red blood cell (RBC) aggregability and deformability among obese patients qualified for bariatric surgery and its correlation with plasma lipid concentration. We studied 40 morbidly obese patients who were qualified for bariatric surgery: mean age was 43.5 ± 11.3 years, and mean body mass index (BMI) was 48.9 ± 7.7 kg/m2.The RBC deformability and aggregation parameters: aggregation index (AI), syllectogram amplitude (AMP) and aggregation half-time (t1/2) were measured by Laser-assisted Optical Rotational Cell Analyser - LORCA. Elongation index of RBC was significantly lower in obese patients than in the control group (P < 0.001) in 3.16–60.03 Pa shear stresses. Correlations between elongation index and triglyceride levels ranged between 0.42 to 0.44 (P < 0.05). AI was significantly higher in the obese patients (P < 0.001), t1/2 and the AMP were decreased (P < 0.001) compared to the control group. The RBC aggregation index correlated positively with total cholesterol level (r = 0.61, P < 0.05), non-HDL cholesterol level (r = 0.54, P < 0.05) and BMI (r = 0.48, P < 0.05). Negative correlation presented t1/2 with total cholesterol (r = −0.64, P < 0.05), non-HDL cholesterol (r = −0.51, P < 0.05) and BMI (r= −0.59, P < 0.05). Obesity is associated with RBC rheological disturbances expressed by a decrease in RBC deformability, increased total aggregation extent and the alteration of kinetics of RBC aggregation. These results may suggest the necessity of introducing treatment forms to correct erythrocyte rheological properties, which may improve the blood-flow condition in the microcirculation and prevent postoperative complications after bariatric surgery.

BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake

Abstract: Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

Physiological and pathophysiological roles of NAMPT and NAD metabolism

Abstract: Nicotinamide phosphoribosyltransferase (NAMPT) is a regulator of the intracellular nicotinamide adenine dinucleotide (NAD) pool. NAD is an essential coenzyme involved in cellular redox reactions and is a substrate for NAD-dependent enzymes. In various metabolic disorders and during ageing, levels of NAD are decreased. Through its NAD-biosynthetic activity, NAMPT influences the activity of NAD-dependent enzymes, thereby regulating cellular metabolism. In addition to its enzymatic function, extracellular NAMPT (eNAMPT) has cytokine-like activity. Abnormal levels of eNAMPT are associated with various metabolic disorders. NAMPT is able to modulate processes involved in the pathogenesis of obesity and related disorders such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) by influencing the oxidative stress response, apoptosis, lipid and glucose metabolism, inflammation and insulin resistance. NAMPT also has a crucial role in cancer cell metabolism, is often overexpressed in tumour tissues and is an experimental target for antitumour therapies. In this Review, we discuss current understanding of the functions of NAMPT and highlight progress made in identifying the physiological role of NAMPT and its relevance in various human diseases and conditions, such as obesity, NAFLD, T2DM, cancer and ageing.

Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB.

Abstract: The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.

Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.

Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m2. However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m2) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.