Piotr Kocełak

Gut microbiota, microinflammation, metabolic profile, and zonulin concentration in obese and normal weight subjects.

The association between gut microbiota and circulating zonulin level, a marker of intestinal permeability, has not been studied yet. The aim of the study is the assessment of plasma zonulin, haptoglobin and proinflammatory cytokines (TNF-α and IL-6) levels in relation to composition of gut microbiota in obese and normal weight subjects. Circulating inflammation markers, such as TNF-α, sTNFR1, sTNFR2, IL-6, zonulin, and haptoglobin levels were measured and semiquantitative analysis of gut microbiota composition was carried out in 50 obese and 30 normal weight subjects without concomitant diseases. Higher circulating zonulin, TNF-α, sTNFR1, sTNFR2, and IL-6 levels were found in the obese subjects. Plasma zonulin level correlated positively with age (r = 0.43, P < 0.001), body mass (r = 0.30, P < 0.01), BMI (r = 0.33, P < 0.01), fat mass and fat percentage (r = 0.31, P < 0.01 and r = 0.23, P < 0.05, resp.). Positive correlations between bacterial colony count and sTNFR1 (r = 0.33, P < 0.01) and plasma zonulin (r = 0.26, P < 0.05) but not haptoglobin levels were found. Additionally, plasma zonulin level was proportional to daily energy intake (r = 0.27, P < 0.05) and serum glucose concentration (r = 0.18, P < 0.05) and inversely proportional to diet protein percentage (r = −0.23, P < 0.05). Gut microbiota-related systemic microinflammation in the obese is reflected by circulating zonulin level, a potential marker of interstitial permeability.

Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome

Introduction Visfatin is an adipokine secreted by visceral adipose tissue with insulin-mimetic properties. Higher circulating visfatin levels were reported in type 2 diabetes. The aim of this study was to analyse circulating visfatin and insulin levels and the visfatin/insulin ratio in obese women with and without metabolic syndrome (MetS). Material and methods The study involved 92 obese women. Subjects were diagnosed with MetS according to IDF 2005 criteria. The MetS group consisted of 71 subjects (age: 52.8 ±9.4 years, body mass index [BMI]: 39.1 ±5.6 kg/m2, waist circumference: 109.6 ±11.4 cm and fat mass: 52.0 ±12.8 kg) while the non-MetS group consisted of 21 subjects (age: 51.7 ±9.5 years, BMI: 36.3 ±5.2 kg/m2, waist circumference: 104.7 ±11.0 cm and fat mass: 45.2 ±10.7 kg). In addition to anthropometric measurements and assessment of serum glucose and lipids, plasma concentrations of visfatin were estimated by enzyme-linked immunosorbent assay (ELISA) and of insulin by radioimmunoassay (RIA). Homeostatic model assessment insulin resistance (HOMA-IR) and visfatin/insulin ratio were calculated. Results In the MetS group significantly higher (p < 0.01) plasma concentrations of insulin and HOMA-IR values but similar visfatin levels were observed than in the non-MetS group. As a consequence of the significantly higher plasma insulin concentration the visfatin/insulin ratio was significantly lower in the MetS group (p < 0.05). The visfatin/insulin ratio correlated inversely with anthropometric parameters such as body mass, BMI, body fat and waist circumference (r = –0.41, p = 0.0003; r = –0.42, p = 0.0002; r = –0.29, p = 0.01; r = –0.23, p = 0.04, respectively). Conclusions We conclude that the visfatin/insulin ratio declining with increasing visceral obesity may predispose to the development of insulin resistance.

Body fat changes and activity of tumor necrosis factor α system—a 5-year follow-up study

Obesity is associated with subclinical, chronic, and systemic immune activation characterized by increased serum concentration of proinflammatory cytokines released by adipose tissue. The aim of the present study was to determine the relationship between stage of development of obesity and changes in activity of tumor necrosis factor (TNF) system during 5-year follow-up observation. One hundred fifty-four women--102 obese, 24 overweight, and 28 lean--without concomitant diseases were examined for the first time from 2000 to 2001. After 5 years, 57 obese, 12 overweight, and 14 lean subjects were reexamined. In addition to anthropometric measurements, body composition was determined by the bioimpedance method; and serum concentrations of glucose, lipids, insulin, TNF-α, and soluble TNF receptors (sTNFRs) were measured. Only reexamined subjects were included in the analysis. After 5 years, fat mass increased significantly in 46 (66.7%) overweight or obese women and in all lean subjects (39.0 ± 12.3 vs 47.3 ± 13.6 kg, P < .001; 14.8 ± 3.7 vs 20.6 ± 5.4 kg, P < .01, respectively), whereas it decreased in 23 (33.3%) overweight or obese subjects (41.3 ± 12.5 vs 37.2 ± 14.0 kg, P < .005). The TNF-α levels increased significantly only in lean women (3.1 ± 3.0 vs 5.6 ± 2.0 pg/mL, P < .005), but remained unchanged in overweight and obese subjects regardless of fat mass changes. Serum concentrations of sTNFR1 and sTNFR2 decreased by 71% and 25% in obese, by 104% and 21% in overweight, and by 31% and 32% in lean group, respectively. The increase of plasma TNF-α level is an early event in abdominal fat accumulation. It seems that further fat mass gain does not enhance circulating TNF-α levels.

Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population

OBJECTIVE Fibroblast growth factor 23 (FGF23) is a phosphaturic agent involved in calcium-phosphate homeostasis. Recent findings show that iron deficiency and inflammation regulate FGF23 release and/or biodegradation. Iron deficiency is frequently observed in the elderly, therefore the aim of this study was to find out if iron deficiency is independent from low grade inflammatory factors affecting both forms of FGF23 that are detectable in circulation in a large population-based study of elderly subjects. DESIGN AND METHODS The analysis included 3780 elderly (1798 females) PolSenior study participants and assessed levels of phosphorus, calcium, iron, ferritin, interleukin 6, C-reactive protein (hs-CRP), intact (iFGF23), and c-terminal FGF (cFGF23). The analysis was performed for all subjects and terciles of serum iron levels in relation to hs-CRP were calculated. RESULTS The highest plasma cFGF23 and iFGF23 concentrations were found in subjects with the lowest serum iron levels (p<0.001). The effect of low grade inflammation was markedly weaker and affected only iFGF23 levels. The adjusted serum levels of hs-CRP, iPTH, phosphorus, and 25-(OH)-D3 analysis revealed that plasma iFGF23 and cFGF23 levels were almost unchanged up to a serum iron level of 59.3 ng/mL and 57.3 ng/mL respectively and then were nearly linearly increasing by 0.285 pg/mL and 3.742 RU/mL for each unit of serum iron increase. CONCLUSIONS Low iron levels are associated with increased levels of both cFGF23 and iFGF23, independent of low grade inflammation. A similar analysis of cFGF23 and iFGF23 does not suggest enhanced biodegradation of iFGF23 induced by iron deficiency.

Psychological Disturbances and Quality of Life in Obese and Infertile Women and Men

Anovulatory cycles and endometriosis are the main causes of female infertility. The most frequently anovulatory cycles are related to polycystic ovary syndrome (PCOS) commonly associated with obesity and hormonal disturbances in the course of obesity. Recently published studies revealed that infertility affects about one in six couples during their lifetime and is more frequent in obese. Obesity is also associated with male infertility related to erectile dysfunction, hormonal disturbances and lower semen quality. Any of these above mentioned disorder is the important risk factor of psychological disturbances and poor quality of life among women and men in the reproductive age. On the other hand the mood disorders may exacerbate the hormonal disturbances and worsen the effectiveness of infertility management. Infertility, its therapy with accompanying psychological disturbances may also significantly affect the partners relationships. The review summarize the results described in the current literature on the association between obesity and infertility and psychological disturbances as well as their impact on quality of life and sexual functioning in women and men. Moreover, the impact of infertility and psychological disturbances on partners relationships is discussed.

Fibroblast growth factor 23 (FGF23) and early chronic kidney disease in the elderly

BACKGROUND Better biomarkers of CKD reflecting responses to decreased glomerular filtration rate (GFR) are needed. We determined the value of estimated GFR (eGFR) as a threshold for the increase of plasma cFGF23 (C-terminal) and intact fibroblast growth factor-23 (iFGF23) (intact) concentrations in the course of chronic kidney disease (CKD) and compared this eGFR value with values related to increased serum intact parathyroid hormone (iPTH) or phosphorus concentrations in an elderly population. METHODS We measured plasma iFGF23, cFGF23, serum phosphorus, calcium, albumin, creatinine, urea, cystatin C, iPTH and vitamin 25-OH-D3 in 3780 population-based study participants aged ≥ 65 years. RESULTS Serum phosphorus concentrations hardly increased until mean eGFR reached 47.3 ± 4.7 mL/min/1.73 m(2) but then increased exponentially. Similarly, both iPTH and iFGF23 increased slightly in early CKD but then increased exponentially when eGFR reached 55.0 ± 4.2 mL/min/1.73 m(2) for iPTH and 51.6 ± 5.7 mL/min/1.73 m(2) for iFGF23. The departure point for exponential increases in cFGF23 preceded those for iPTH and iFGF23 and occurred at a mean eGFR of 57.7 ± 7.8 mL/min/1.73 m(2). The prevalence of increased iFGF23 occurred at a remarkably higher eGFR value than that of cFGF23 across the CKD stages. CONCLUSIONS The increase in cFGF23 preceded both the increase in iPTH and iFGF23 as eGFR declined. Increased plasma iFGF23 level did not precede the rise in serum iPTH concentrations and did not occur before stage-3 CKD in elderly persons. However, cFGF23 was not an early marker of CKD in the elderly subjects.

The role of gut microbiota in the pathogenesis of obesity

Obesity is a disease that develops as a result of long-term positive energy balance. In recent years, the influence of gut microflora composition, as a potential factor affecting the energy balance and contributing to fat accumulation, has been studied. It seems that bacteria can affect host energy balance through several mechanisms, such as increased fermentation of undigested polysaccharides and obtaining extra energy from the portion of food, reduced expression of FIAF (fasting-induced adipocyte factor) in the enterocytes with inhibitory activity towards intestinal lipoprotein lipase, and the increased release of peptide YY that slows the intestinal motility. It is also believed that changes in the composition of gut microflora may be one of the factors that induce systemic microinflammation in the obese, an important link in the pathogenesis of obesity related complications, including dyslipidaemia, hypertension and type 2 diabetes. However, the results of previous studies are inconclusive. Many of them have been carried out in an animal model and were not confirmed in studies involving humans. These discrepancies may be due to different composition of the diet, distinct physiological gut microflora and the methodology used in these studies. The present article reviews the current literature on the potential role of gut microflora in the pathogenesis of obesity.

Is chronic inflammation a possible cause of obesity-related depression?

Adult obesity has been associated with depression, especially in women. Whether depression leads to obesity or obesity causes depression is unclear. Chronic inflammation is observed in obesity and depression. In 63 obese women without additional diseases depression level was assessed with the Becks questionnaire. After evaluation of depression level study group was divided into groups according to the mood status (A—without depression, B—mild depression, and C—severe depression), and serum concentration of TNF-α, sTNFs, leptin, and IL-6 were measured by ELISA. No differences in age, body mass, BMI, and body composition were observed in study groups. We did not observe differences of serum concentrations of TNF-α, sTNFRs, leptin, and IL-6 between subgroup A and subgroups B and C. It seems that circulating adipokines did not exert influence on depression levels in obese women.

Long-term effects of lipase inhibition by orlistat on gastric emptying and orocecal transit time of a solid meal

BackgroundWe assessed the impact of a prolonged lipase inhibition upon gastric emptying (GE) and orocecal transit time (OCTT) of a 355-kcal low-fat solid meal.MethodsIn double-blind manner, 40 obese women BMI > 30 kg/m2, randomly allocated into two equal groups, took orally t.i.d. 120 mg orlistat or placebo during 8 weeks of a weight-reducing management. At randomization and after 2 months, GE was measured simultaneously with OCTT by means of a 13C-octanoic acid and a hydrogen breath test, respectively. Lipolytic activity was evaluated with a 13C-mixed triglyceride breath test (13C-MTGBT).ResultsA profound lipase inhibition by orlistat was confirmed by a 79.5% ± 16.9% reduction of the cumulative 6-h 13C recovery with 13CMTGBT. GE remained unchanged either in the orlistat (T1/2, 188 ± 35 min start versus 198 ± 36 min end) or the placebo (T1/2, 191 ± 35 min start versus 180 ± 39 min end) group. OCTT increased from 208 ± 54 min to 271 ± 64 min (P < 0.01) after orlistat treatment and did not change significantly (216 ± 76 vs. 234 ± 72 min) in the placebo group.ConclusionsNo adverse effect on the GE and a moderate prolongation of the OCTT of a low-fat solid meal is to be expected under a prolonged treatment with orlistat at a typical dosage regimen.

Long-term inhibition of intestinal lipase by orlistat improves release of gut hormones increasing satiety in obese women

BACKGROUND Reduced postprandial secretion of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin, and increased hunger was reported after a single dose of orlistat, an inhibitor of intestinal lipase. As yet, the influence of long-term therapy with orlistat on PYYand GLP-1 release has not been studied. Our study was aimed at assessing the influence of 8-week therapy with orlistat as a component of a weight loss program on pre-prandial circulating PYY and GLP-1 levels. METHODS Forty obese women, without concomitant diseases, were randomly allocated to groups receiving orlistat or placebo during an 8-week weight management program. Body mass, body composition and plasma levels of PYY, GLP-1 and insulin (for QUICKI calculation) were determined prior to and at the end of therapy. RESULTS Women treated with orlistat obtained significantly greater body and fat mass loss than those receiving placebo (9.0 ± 3.1 vs. 5.9 ± 3.2% and 21.9 ± 10.9 vs. 7.4 ± 15.6%, respectively). Only in those treated with orlistat a slight, but significant increase of the QUICKI was found (8.0 ± 16.5 vs. -0.1 ± 12.7 %, respectively). Weight loss was followed by a significant increase of plasma levels of PYY and GLP-1 in group treated with orlistat, and was about 2-times greater than receiving placebo. The increase was independent of body mass changes. CONCLUSION The long-term inhibition of intestinal lipase by orlistat increases the pre-prandial levels of GLP-1 and PYY, independent of body mass changes. Therefore, it seems that long-term treatment with orlistat may exert hunger suppressing and insulin sensitizing incretin effect beyond weight reduction.