Hana Papežová

Plasma Concentrations of Fibroblast Growth Factors 19 and 21 in Patients with Anorexia Nervosa

CONTEXT Fibroblast growth factor 19 (FGF19) and FGF21 are novel metabolic regulators that improve insulin sensitivity and decrease adiposity in mice. However, little is known about the nutritional regulation of these factors in humans. OBJECTIVE The objective of this study was to measure plasma FGF19 and FGF21 levels in patients with anorexia nervosa (AN) and to explore its relationship with anthropometric and endocrine parameters. DESIGN This was a single-center cross-sectional study. SETTING The study was performed in a university hospital. PATIENTS Seventeen untreated women with a restrictive type of AN and 17 healthy women (control group) were included. MAIN OUTCOME MEASURES Fasting plasma FGF19 and FGF21, serum insulin, leptin, soluble leptin receptor, adiponectin, resistin, and C-reactive protein were the main outcome measures. RESULTS Plasma FGF19 levels did not significantly differ between the groups studied, whereas plasma FGF21 levels were significantly reduced in AN relative to the control group. Plasma FGF21 positively correlated with body mass index and serum leptin and insulin and was inversely related to serum adiponectin in both groups. In contrast, plasma FGF19 was not related to any of parameters studied. Partial realimentation significantly reduced plasma FGF21 levels in AN. CONCLUSION Circulating levels of FGF21 but not FGF19 are strongly related to body weight and serum levels of leptin, adiponectin, and insulin in both anorectic and normal-weight women. We suggest that reduced plasma FGF21 levels could be involved in the pathophysiology of AN or in a complex adaptive response to this disease.

Cholesterol-lowering therapy evokes time-limited changes in serotonergic transmission

A number of studies have reported an increased risk for violent deaths and depression in subjects with reduced serum cholesterol concentrations. Links with hypothesized impairment of serotonin neurotransmission have not been satisfactorily tested. In this investigation, the serum and membrane cholesterol, microviscosity of erythrocyte membranes, platelet serotonin uptake, and clinical parameters were determined during pharmacotherapy of 17 hypercholesterolemic patients. A significant decrease in serum cholesterol and a nonsignificant decrease in membrane cholesterol concentration were found after 2 months of simvastatin therapy. Serotonin transporter (SERT) activity was significantly increased following 1 month of simvastatin; the tendency to decrease the initial increase in SERT activity was evident following 2 months of therapy. Both membrane cholesterol and SERT activity returned to pre-treatment levels after more than 1 year of therapy. Microviscosity of plasma membranes, impulsivity, empathy, adventure, sensation seeking, and depressed mood were not markedly changed. These data indicate that long-term therapy has different effects on serotonin transmission from short-term (1- to 2-month) therapy. A significant increase in SERT activity was detected only during the first month of simvastatin therapy. This finding suggests that within this period some patients could be vulnerable to depression, violence, or suicide.

Relationship of serum leptin levels and selected nutritional parameters in patients with protein-caloric malnutrition

Leptin is a protein hormone produced by adipocytes that reflects the body fat content, i.e., its serum concentration in healthy individuals positively correlates with the body mass index and body fat content. Serum leptin levels are lower in both patients with anorexia nervosa and protein-caloric malnutrition caused by chronic non-malignant illnesses. The aim of the present study was to compare serum leptin levels and selected, routinely used nutritional parameters in women with anorexia nervosa (n = 17), severely malnourished patients with short bowel syndrome (n = 13), and control non-obese healthy women (n = 17) to clarify the relation between selected nutritional parameters and serum leptin levels. We found that serum leptin levels in the anorexia nervosa and short bowel syndrome groups were significantly lower than those in the control group (in ng/mL: 3.63 +/- 1.64 and 2.59 +/- 1.17 versus 12.06 +/- 7.59, respectively). Protein malnutrition expressed by decrease in serum concentrations of total protein, albumin, and prealbumin was more pronounced in the short bowel syndrome group. Triceps skin fold, arm muscle circumference, and body mass index were significantly lower in the patient group than in the control group and did not significantly differ between the short bowel syndrome and anorexia nervosa groups. No significant difference in serum leptin concentration between the short bowel syndrome and anorexia nervosa groups was found. Serum leptin levels correlated positively with body mass index and triceps skin fold in the control and anorexia nervosa groups but not in the short bowel syndrome group. We conclude that serum leptin levels in patients with anorexia nervosa and short bowel syndrome are significantly lower than in healthy individuals and have no statistically significant relation to serum total protein, abumin, and prealbumin.

Leptin concentrations in the abdominal subcutaneous adipose tissue of patients with anorexia nervosa assessed by in vivo microdialysis

OBJECTIVE The adipocyte-derived hormone leptin is involved in energy metabolism and body weight regulation. Plasma leptin concentrations are significantly reduced in patients with anorexia nervosa (AN) and with severe malnutrition. Whether reduced plasma leptin is reflected by its decreased production by the adipose tissue is unknown. METHODS In the present study we measured leptin concentrations locally in the abdominal subcutaneous adipose tissue of 9 female AN patients and 11 healthy controls by in vivo microdialysis. RESULTS Adipose tissue free leptin levels were not different in patients with AN compared to controls (2.59+/-1.99 vs 2.36+/-0.25 ng/ml, P>0.05). Plasma leptin soluble receptor (sOb-R) levels were significantly higher in patients with AN than in healthy subjects (58.05+/-38.69 vs 12.79+/-5.08 U/ml, P<0.01). The area of adipocyte in AN was considerably smaller than in the controls (183+/-104.01 microm2 compared to 2145.8+/-1003.41). CONCLUSIONS We conclude that decreased plasma leptin levels in patients with AN are not directly related to dialysate leptin levels in the abdominal subcutaneous adipose tissue.

Association of macrophage inhibitory cytokine-1 with nutritional status, body composition and bone mineral density in patients with anorexia nervosa: the influence of partial realimentation.

BackgroundMacrophage inhibitory cytokine-1 (MIC-1) is a key inducer of cancer-related anorexia and weight loss. However, its possible role in the etiopathogenesis of nutritional disorders of other etiology such as anorexia nervosa (AN) is currently unknown.MethodsWe measured fasting serum concentrations of MIC-1 in patients with AN before and after 2-month nutritional treatment and explored its relationship with nutritional status, metabolic and biochemical parameters. Sixteen previously untreated women with AN and twenty-five normal-weight age-matched control women participated in the study. We measured serum concentrations of MIC-1 and leptin by ELISA, free fatty acids by enzymatic colorimetric assay, and biochemical parameters by standard laboratory methods; determined resting energy expenditure by indirect calorimetry; and assessed bone mineral density and body fat content by dual-energy X-ray absorptiometry. ANOVA, unpaired t-test or Mann-Whitney test were used for groups comparison as appropriate. The comparisons of serum MIC-1 levels and other studied parameters in patients with AN before and after partial realimentation were assessed by paired t-test or Wilcoxon Signed Rank Test as appropriate.ResultsAt baseline, fasting serum MIC-1 concentrations were significantly higher in patients with AN relative to controls. Partial realimentation significantly reduced serum MIC-1 concentrations in patients with AN but it still remained significantly higher compared to control group. In AN group, serum MIC-1 was inversely related to Buzby nutritional risk index, serum insulin-like growth factor-1, serum glucose, serum total protein, serum albumin, and lumbar bone mineral density and it significantly positively correlated with the duration of AN and age.ConclusionsMIC-1 concentrations in AN patients are significantly higher relative to healthy women. Partial realimentation significantly decreased MIC-1 concentration in AN group. Clinical significance of these findings needs to be further clarified.

Angiopoietin-like protein 3 and 4 in obesity, type 2 diabetes mellitus, and malnutrition: the effect of weight reduction and realimentation

BackgroundAngiopoietin-like proteins (ANGPTLs) 3 and 4 are circulating factors that participate in the regulation of lipid and glucose metabolism.Subjects and methodsWe measured serum ANGPTL3 and 4 levels in 23 patients with obesity, 40 patients with obesity and type 2 diabetes mellitus (T2DM), 22 patients with anorexia nervosa (AN), 15 subjects undergoing 72-h fasting, and 12 patients with short bowel syndrome (SBS), and their changes after very-low-calorie diet (VLCD), bariatric surgery, partial realimentation, acute fasting, and parenteral nutrition in order to assess their possible role in metabolic regulations.ResultsSerum ANGPTL4 levels were higher in obese subjects without/with T2DM (94.50 ± 9.51 and 134.19 ± 7.69 vs. 50.34 ± 4.22 ng/ml, p < 0.001) and lower in subjects with AN relative to healthy control subjects (38.22 ± 4.48 vs. 65.80 ± 7.98 ng/ml, p = 0.002), while serum ANGPTL3 levels demonstrated inverse tendency. Nutritional status had no effect on ANGPTL3 and 4 mRNA expression in adipose tissue. Fasting decreased ANGPTL3 and increased ANGPTL4 levels, while VLCD reduced only ANGPTL3. Bariatric surgery and realimentation of AN or SBS patients had no effect on either ANGPTL. Multiple regression analysis identified BMI as an independent predictor of ANGPTL3; and BMI and HbA1c as independent predictors of ANGPTL4, respectively.ConclusionsTaken together, our data suggest that serum ANGPTL3 and 4 levels are influenced by nutritional status and fasting and could be involved in the metabolic disturbances present in obesity and AN.