Publications by authors named "Małgorzata Malczewska-Malec"

35 Publications

Epigenetic Regulation of Processes Related to High Level of Fibroblast Growth Factor 21 in Obese Subjects.

Genes (Basel) 2021 Feb 21;12(2). Epub 2021 Feb 21.

Department of Clinical Biochemistry, Jagiellonian University Medical College, 15a Kopernika Street, 31-501 Krakow, Poland.

We hypothesised that epigenetics may play an important role in mediating fibroblast growth factor 21 (FGF21) resistance in obesity. We aimed to evaluate DNA methylation changes and miRNA pattern in obese subjects associated with high serum FGF21 levels. The study included 136 participants with BMI 27-45 kg/m. Fasting FGF21, glucose, insulin, GIP, lipids, adipokines, miokines and cytokines were measured and compared in high serum FGF21 ( = 68) group to low FGF21 ( = 68) group. Human DNA Methylation Microarrays were analysed in leukocytes from each group ( = 16). Expression of miRNAs was evaluated using quantitative PCR-TLDA. The study identified differentially methylated genes in pathways related to glucose transport, insulin secretion and signalling, lipid transport and cellular metabolism, response to nutrient levels, thermogenesis, browning of adipose tissue and bone mineralisation. Additionally, it detected transcription factor genes regulating FGF21 and fibroblast growth factor receptor and vascular endothelial growth factor receptor pathways regulation. Increased expression of hsa-miR-875-5p and decreased expression of hsa-miR-133a-3p, hsa-miR-185-5p and hsa-miR-200c-3p were found in the group with high serum FGF21. These changes were associated with high FGF21, VEGF and low adiponectin serum levels. Our results point to a significant role of the epigenetic regulation of genes involved in metabolic pathways related to FGF21 action.
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http://dx.doi.org/10.3390/genes12020307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926457PMC
February 2021

DNA methylation microarrays identify epigenetically regulated lipid related genes in obese patients with hypercholesterolemia.

Mol Med 2020 10 7;26(1):93. Epub 2020 Oct 7.

Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15a, 31-501, Kraków, Poland.

Background: Epigenetics can contribute to lipid disorders in obesity. The DNA methylation pattern can be the cause or consequence of high blood lipids. The aim of the study was to investigate the DNA methylation profile in peripheral leukocytes associated with elevated LDL-cholesterol level in overweight and obese individuals.

Methods: To identify the differentially methylated genes, genome-wide DNA methylation microarray analysis was performed in leukocytes of obese individuals with high LDL-cholesterol (LDL-CH, ≥ 3.4 mmol/L) versus control obese individuals with LDL-CH, < 3.4 mmol/L. Biochemical tests such as serum glucose, total cholesterol, HDL cholesterol, triglycerides, insulin, leptin, adiponectin, FGF19, FGF21, GIP and total plasma fatty acids content have been determined. Oral glucose and lipid tolerance tests were also performed. Human DNA Methylation Microarray (from Agilent Technologies) containing 27,627 probes for CpG islands was used for screening of DNA methylation status in 10 selected samples. Unpaired t-test and Mann-Whitney U-test were used for biochemical and anthropometric parameters statistics. For microarrays analysis, fold of change was calculated comparing hypercholesterolemic vs control group. The q-value threshold was calculated using moderated Student's t-test followed by Benjamini-Hochberg multiple test correction FDR.

Results: In this preliminary study we identified 190 lipid related CpG loci differentially methylated in hypercholesterolemic versus control individuals. Analysis of DNA methylation profiles revealed several loci engaged in plasma lipoprotein formation and metabolism, cholesterol efflux and reverse transport, triglycerides degradation and fatty acids transport and β-oxidation. Hypermethylation of CpG loci located in promoters of genes regulating cholesterol metabolism: PCSK9, LRP1, ABCG1, ANGPTL4, SREBF1 and NR1H2 in hypercholesterolemic patients has been found. Novel epigenetically regulated CpG sites include ABCG4, ANGPTL4, AP2A2, AP2M1, AP2S1, CLTC, FGF19, FGF1R, HDLBP, LIPA, LMF1, LRP5, LSR, NR1H2 and ZDHHC8 genes.

Conclusions: Our results indicate that obese individuals with hypercholesterolemia present specific DNA methylation profile in genes related to lipids transport and metabolism. Detailed knowledge of epigenetic regulation of genes, important for lipid disorders in obesity, underlies the possibility to influence target genes by changing diet and lifestyle, as DNA methylation is reversible and depends on environmental factors. These findings give rise for further studies on factors that targets methylation of revealed genes.
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http://dx.doi.org/10.1186/s10020-020-00220-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539457PMC
October 2020

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis.

Nutrients 2020 Feb 13;12(2). Epub 2020 Feb 13.

Department of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, Poland.

Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25-40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [β = 0.16 (confidence interval (CI): 0.01-0.32)], triglycerides [β = 0.21 (95% CI: 0.06-0.36], and FGF-21 [β = 0.20 (95%CI: 0.03-0.37)]; and postprandial GIP with GGT [β = 0.17 (95%CI: 0.03-0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02-5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut-liver cross-talk.
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http://dx.doi.org/10.3390/nu12020476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071278PMC
February 2020

Effect of insulin resistance on whole blood mRNA and microRNA expression affecting bone turnover.

Eur J Endocrinol 2019 Nov;181(5):525-537

Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.

Objective: To evaluate the effect of insulin resistance in obesity on the expression in whole blood of mRNA and miRNA affecting bone homeostasis as well as to estimate the influence of oral glucose load (OGTT) on serum osteocalcin concentration in obese individuals with and without insulin resistance.

Design: Cross-sectional study.

Methods: Carboxylated (cOC), undercarboxylated (ucOC) and total osteocalcin were measured by ELISA in the serum of obese subjects with insulin resistance (n = 41) and obese subjects without insulin resistance (n = 41) (control group) during OGTT. Analysis of gene expression (microarray) and miRNAs (real-time PCR) was performed in venous blood (representating samples) collected before OGTT from obese with insulin resistance and controls.

Results: Obese subjects with insulin resistance (higher HOMA-IR and lower oral glucose insulin sensitivity index) presented significantly increased expression of WNT signalling inhibitors (DKK1, DKK2, SOST, SFRP1) and downregulation of the key factor in WNT signalling - β catenin participating in osteoblasts differentiation. Expression of miRNA involved in osteoblastogenesis was also inhibited (miR-29b, miR-181a, miR-210, miR-324-3p). During OGTT, contrary to the control group, subjects with insulin resistance presented suppression of cOC and total OC decrease after 1 and 2 h of oral glucose load.

Conclusions: Obese subjects with insulin resistance may have defects in osteoblastogenesis that was demonstrated via key signalling molecules mRNA downregulation, and increased expression of WNT antagonists as well as inhibition of expression of miRNA participating in the regulation of osteoblast differentiation. Disturbed osteoblastogenesis in insulin-resistant subjects results in the suppression of blood carboxylated and total osteocalcin decrease during OGTT.
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http://dx.doi.org/10.1530/EJE-19-0542DOI Listing
November 2019

Case report of dysregulation of primary bile acid synthesis in a family with X-linked adrenoleukodystrophy.

Medicine (Baltimore) 2018 Dec;97(49):e13353

Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.

Rationale: X-linked adrenoleukodystrophy (X-ALD) is a rare disorder caused by mutations in the ABCD1 gene, coding for peroxisomal membrane transporter adrenoleukodystrophy (ALD) protein. The disease is characterized by accumulation of very long chain fatty acids (VLCFAs) in tissues. Adult adrenomyeloneuropathy (AMN) and the cerebral inflammatory form of ALD are the main phenotypes presenting various symptoms.

Patient Concerns: We report a case of 37-year-old patient with diagnosis of X-ALD, confirmed based on elevated VLCFA concentrations and genetic testing of ABCD1 gene. The complete clinical picture in the patient indicates AMN phenotype with cerebral involvement.

Diagnoses: The reduced synthesis of unconjugated cholic and chenodeoxycholic acids, and the reduction to 28% to 29% of peroxisomal beta-oxidation of behenic acid and normal peroxisomal metabolism of pristanic and palmitic acid were observed in the X-ALD patient. Sanger sequencing of major genes involved in primary bile acid (BA) synthesis failed to identify pathogenic mutations of the investigated set of genes.

Interventions: Plasma concentrations of BAs, VLCFAs, and beta-oxidation of C22:0, C16:0, and pristanic acid were studied in primary skin fibroblasts of the patient. In addition, we performed sequencing of the ABCD1, ABCD3, CYP7A1, CYP7B1, CYP27A1, HSD3B7, AKR1D1, and SLC27A5 genes in the X-ALD family.

Outcomes: In the Polish family affected with AMN a dysregulation of the primary BA synthesis pathway was found.

Lessons: We have demonstrated the coincidence of the adult form of X-ALD with abnormalities in BA synthesis. We suggest that decreased synthesis of BAs may be an additional dysfunction as a consequence of the ABCD1 c.659T>C, p.(Leu220Pro) mutation and may be further evidence that disturbed cholesterol metabolism is important in the pathology of ALD.
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http://dx.doi.org/10.1097/MD.0000000000013353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310492PMC
December 2018

High Fat Mixed Meal Tolerance Test Leads to Suppression of Osteocalcin Decrease in Obese Insulin Resistant Subjects Compared to Healthy Adults.

Nutrients 2018 Nov 1;10(11). Epub 2018 Nov 1.

Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15a, 31-501 Krakow, Poland.

Nutrients influence bone turnover. Carboxylated osteocalcin (Gla-OC) participates in bone formation whereas its undercarboxylated form (Glu-OC) acts as a hormone in glucose metabolism. The aim of the study was to determine the responses of Gla-OC, Glu-OC, and total-OC (calculated as the sum of Gla-OC and Glu-OC) to a high fat mixed meal tolerance test (HFMTT) in non-obese (body mass index (BMI) < 30 kg/m², = 24) and obese subjects (30 < BMI < 40 kg/m², = 70) (both sexes, aged 25⁻65 years). Serum Gla-OC and Glu-OC were measured at baseline as well as at 2 and 6 h during a HFMTT by enzyme-linked immunosorbent assay (ELISA). Baseline Gla-OC, Glu-OC, and total-OC levels were lower in obese individuals compared to non-obese participants ( = 0.037, = 0.016 and = 0.005, respectively). The decrease in Gla-OC and total-OC, but not in Glu-OC, concentrations during the HFMTT was suppressed in obese, but not in non-obese controls ( < 0.05, < 0.01, = 0.08, respectively). Subjects with the highest homeostatic model assessment for insulin resistance (HOMA-IR) index values had a less pronounced decrease in total-OC compared to patients with values of HOMA-IR index in the 1st quartile ( < 0.05). Net incremental area under Gla-OC inversely correlated with adiponectin (rho = -0.35, = 0.001). Increase in insulin sensitivity and adiponectin level in obese subjects could beneficially influence postprandial bone turnover expressed by osteocalcin concentration.
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http://dx.doi.org/10.3390/nu10111611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267021PMC
November 2018

Relation of the protein glycation, oxidation and nitration to the osteocalcin level in obese subjects.

Acta Biochim Pol 2017 28;64(3):415-422. Epub 2017 Jul 28.

Department of Clinical Biochemistry, Jagiellonian University Medical College, Kraków, Poland.

Carboxylated osteocalcin (Gla-OC) contributes to the bone formation, whereas its undercarboxylated form (Glu-OC) takes part in the energy metabolism. In vitro studies had shown that treatment of osteoblast-like cells with advanced glycation end product-modified bovine serum resulted in reduced synthesis of collagen 1 and osteocalcin. The aim of this study was to find association between Gla-OC and markers of protein glycation, oxidation and nitration, as well as pro-inflammatory and antioxidant defense markers in obese subjects. Non-obese [(body mass index (BMI)<30 kg/m; n=34)] and obese subjects (30
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http://dx.doi.org/10.18388/abp.2017_1627DOI Listing
February 2018

Glucagon-like peptide-1 receptor agonist stimulates mitochondrial bioenergetics in human adipocytes.

Acta Biochim Pol 2017 19;64(3):423-429. Epub 2017 Aug 19.

Department of Clinical Biochemistry, Medical College, Jagiellonian University, Kraków, Poland.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions. For this purpose, preadipocytes CHUBS7 were differentiated to mature adipocytes and then stimulated with GLP-1RA, exendin-4 at 100 nM for 24 h. Oxygen consumption rates, mitochondrial membrane potential, intracellular ATP (adenosine triphosphate) level, SIRT1 and SIRT3 gene expression and the histone deacetylases' activity were measured. Exendin-4 was found to uncouple mitochondrial electron transport from ATP synthesis, slightly decreasing mitochondrial membrane potential in mature adipocytes. Routine respiration and uncoupled oxy- gen consumption rates were higher in exendin-4 treated adipocytes than in the non-treated cells. The ATP level remained unchanged. Exendin-4 enhanced SIRT1 and SIRT3 genes expression. Histone deacetylases' activity in the nuclear fraction was not affected by exendin-4, although the activity of class III histone deacetylases was increased. All of the effects on mitochondrial bioenergetics induced by exendin-4 were abolished by addition of glucagon-like peptide 1 receptor antagonist. In conclusion, exendin-4 activates the sirtuin pathway and increases energy expenditure in human adipocytes. Our results suggest another mechanism that may be responsible for body weight reduction observed in patients using GLP-1RAs.
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http://dx.doi.org/10.18388/abp.2017_1634DOI Listing
February 2018

Carboxylated and undercarboxylated osteocalcin in metabolic complications of human obesity and prediabetes.

Diabetes Metab Res Rev 2017 03 7;33(3). Epub 2016 Nov 7.

Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.

Background: Carboxylated osteocalcin (Gla-OC) participates in bone remodeling, whereas the undercarboxylated form (Glu-OC) takes part in energy metabolism. This study was undertaken to compare the blood levels of Glu-OC and Gla-OC in nonobese, healthy obese, and prediabetic volunteers and correlate it with the metabolic markers of insulin resistance and early markers of inflammation.

Methods: Nonobese (body mass index [BMI] <30 kg/m ; n = 34) and obese subjects (30
Results: Gla-OC in obese patients was significantly lower compared to nonobese ones (11.36 ± 0.39 vs 12.69 ± 0.90 ng/mL, P = .048) and weakly correlated with hsCRP (r = -0.18, P = .042), visfatin concentration (r = -0.19, P = .033), and BMI (r = -0.17, P = .047). Glu-OC was negatively associated with fasting insulin levels (r = -0.18, P = .049) and reduced in prediabetic individuals compared with healthy obese volunteers (3.04 ± 0.28 vs 4.48 ± 0.57, P = .025).

Conclusions: Decreased blood concentration of Glu-OC may be a selective early symptom of insulin resistance in obesity, whereas the decreased level of Gla-OC seems to be associated with the appearance of early markers of low grade inflammation accompanying obesity.
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http://dx.doi.org/10.1002/dmrr.2862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681168PMC
March 2017

Omega-3 fatty acid supplementation influences the whole blood transcriptome in women with obesity, associated with pro-resolving lipid mediator production.

Biochim Biophys Acta 2016 11 12;1861(11):1746-1755. Epub 2016 Aug 12.

Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland.

The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8g EPA+DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray. Women supplemented with n-3 PUFAs for 3months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-α, NRF2 and NF-κB target genes. N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-α target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes.
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http://dx.doi.org/10.1016/j.bbalip.2016.08.005DOI Listing
November 2016

Dicarbonyl stress in clinical obesity.

Glycoconj J 2016 08 24;33(4):581-9. Epub 2016 Jun 24.

Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, CV2 2DX, UK.

The glyoxalase system in the cytoplasm of cells provides the primary defence against glycation by methylglyoxal catalysing its metabolism to D-lactate. Methylglyoxal is the precursor of the major quantitative advanced glycation endproducts in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. Glyoxalase 1 of the glyoxalase system was linked to anthropometric measurements of obesity in human subjects and to body weight in strains of mice. Recent conference reports described increased weight gain on high fat diet-fed mouse with lifelong deficiency of glyoxalase 1 deficiency, compared to wild-type controls, and decreased weight gain in glyoxalase 1-overexpressing transgenic mice, suggesting a functional role of glyoxalase 1 and dicarbonyl stress in obesity. Increased methylglyoxal, dicarbonyl stress, in white adipose tissue and liver may be a mediator of obesity and insulin resistance and thereby a risk factor for development of type 2 diabetes and non-alcoholic fatty liver disease. Increased methylglyoxal formation from glyceroneogenesis on adipose tissue and liver and decreased glyoxalase 1 activity in obesity likely drives dicarbonyl stress in white adipose tissue increasing the dicarbonyl proteome and related dysfunction. The clinical significance will likely emerge from on-going clinical evaluation of inducers of glyoxalase 1 expression in overweight and obese subjects. Increased transcapillary escape rate of albumin and increased total body interstitial fluid volume in obesity likely makes levels of glycation of plasma protein unreliable indicators of glycation status in obesity as there is a shift of albumin dwell time from plasma to interstitial fluid, which decreases overall glycation for a given glycemic exposure.
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http://dx.doi.org/10.1007/s10719-016-9692-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975769PMC
August 2016

Effect of caloric restriction with or without n-3 polyunsaturated fatty acids on insulin sensitivity in obese subjects: A randomized placebo controlled trial.

BBA Clin 2015 Dec 22;4:7-13. Epub 2015 May 22.

Department of Clinical Biochemistry, Jagiellonian University Medical College, 31-501 Krakow, Poland.

Background: Caloric restriction and n-3 polyunsaturated fatty acid (PUFA) supplementation protect from some of the metabolic complications. The aim of this study was to assess the influence of a low calorie diet with or without n-3 PUFA supplementation on glucose dependent insulinotropic polypeptide (GIP) output and insulin sensitivity markers in obese subjects.

Methods: Obese, non-diabetic subjects (BMI 30-40 kg/m(2)) and aged 25-65 yr. were put on low calorie diet (1200-1500 kcal/day) supplemented with either 1.8 g/day n-3 PUFA (DHA/EPA, 5:1) (n = 24) or placebo capsules (n = 24) for three months in a randomized placebo controlled trial. Insulin resistance markers and GIP levels were analysed from samples obtained at fasting and during an oral glucose tolerance test (OGTT).

Results: Caloric restriction with n-3 PUFA led to a decrease of insulin resistance index (HOMA-IR) and a significant reduction of insulin output as well as decreased GIP secretion during the OGTT. These effects were not seen with caloric restriction alone. Changes in GIP output were inversely associated with changes in red blood cell EPA content whereas fasting GIP level positively correlated with HOMA-IR index. Blood triglyceride level was lowered by caloric restriction with a greater effect when n-3 PUFA were included and correlated positively with fasting GIP level.

Conclusions: Three months of caloric restriction with DHA + EPA supplementation exerts beneficial effects on insulin resistance, GIP and triglycerides.

General Significance: Combining caloric restriction and n-3 PUFA improves insulin sensitivity, which may be related to a decrease of GIP levels.
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http://dx.doi.org/10.1016/j.bbacli.2015.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737910PMC
December 2015

Bipolar spectrum features in obese individuals.

Psychiatr Pol 2015 ;49(5):993-1004

Katedra Psychiatrii UM w Poznaniu.

Unlabelled: AIM : The relationships between obesity and bipolar spectrum disorders (BSD) are unclear. Thus, the aim of our study were to approximate the prevalence of soft bipolar features in patients seeking treatment for obesity.

Methods: We performed a nested case-control study (cases: 90 patients with the mean BMI=38.1±7.0 [range: 30.1-62.5]; controls: 70 healthy volunteers with the mean BMI=21.6±2.1 [range: 18.5-24.9]). The participants were screened for the BSD symptoms with the Mood Disorder Questionnaire.

Results: Patients with obesity were significantly more likely to score ≥7 pts. on the MDQ 25.6% vs. 8.6%; p=0.01). In comparison to non-obese individuals, the obese patients scored significantly higher in MDQ section I and on the MDQ items referring to the 'irritability-racing thoughts' dimension of hypomania. The multiple logistic regression analysis revealed that obesity had been significantly related to the odds of obtaining ≥7 pts. on the MDQ section 1 (odds ratio [OR] = 2.07; 95% confidence interval [CI]: 1.17-3.63), and marginally significantly related to experiencing periods of 'ups' and 'downs'(OR = 1.67; 95% CI: 1.00-2.81).

Conclusions: Our study adds to previous suggestions that obesity may be significantly related to the BSD. However, the clinical implications of this finding need to be determined in further studies, performed in accordance with the paradigm of evidence based medicine (EBM).
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http://dx.doi.org/10.12740/PP/OnlineFirst/32937DOI Listing
December 2016

White adipose tissue reference network: a knowledge resource for exploring health-relevant relations.

Genes Nutr 2015 Jan 3;10(1):439. Epub 2014 Dec 3.

Microbiology & Systems Biology, TNO, Zeist, The Netherlands.

Optimal health is maintained by interaction of multiple intrinsic and environmental factors at different levels of complexity-from molecular, to physiological, to social. Understanding and quantification of these interactions will aid design of successful health interventions. We introduce the reference network concept as a platform for multi-level exploration of biological relations relevant for metabolic health, by integration and mining of biological interactions derived from public resources and context-specific experimental data. A White Adipose Tissue Health Reference Network (WATRefNet) was constructed as a resource for discovery and prioritization of mechanism-based biomarkers for white adipose tissue (WAT) health status and the effect of food and drug compounds on WAT health status. The WATRefNet (6,797 nodes and 32,171 edges) is based on (1) experimental data obtained from 10 studies addressing different adiposity states, (2) seven public knowledge bases of molecular interactions, (3) expert's definitions of five physiologically relevant processes key to WAT health, namely WAT expandability, Oxidative capacity, Metabolic state, Oxidative stress and Tissue inflammation, and (4) a collection of relevant biomarkers of these processes identified by BIOCLAIMS ( http://bioclaims.uib.es ). The WATRefNet comprehends multiple layers of biological complexity as it contains various types of nodes and edges that represent different biological levels and interactions. We have validated the reference network by showing overrepresentation with anti-obesity drug targets, pathology-associated genes and differentially expressed genes from an external disease model dataset. The resulting network has been used to extract subnetworks specific to the above-mentioned expert-defined physiological processes. Each of these process-specific signatures represents a mechanistically supported composite biomarker for assessing and quantifying the effect of interventions on a physiological aspect that determines WAT health status. Following this principle, five anti-diabetic drug interventions and one diet intervention were scored for the match of their expression signature to the five biomarker signatures derived from the WATRefNet. This confirmed previous observations of successful intervention by dietary lifestyle and revealed WAT-specific effects of drug interventions. The WATRefNet represents a sustainable knowledge resource for extraction of relevant relationships such as mechanisms of action, nutrient intervention targets and biomarkers and for assessment of health effects for support of health claims made on food products.
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http://dx.doi.org/10.1007/s12263-014-0439-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252261PMC
January 2015

Obesity and body fat classification in the metabolic syndrome: impact on cardiometabolic risk metabotype.

Obesity (Silver Spring) 2013 Jan;21(1):E154-61

Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.

Objective: Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study).

Design And Methods: Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)).

Results: About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (≥ 30 kg/m(2)) and BF% (≥ 25% (men) and ≥ 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor-α (TNF-α) concentrations were lower post-intervention in NOO individuals compared with OO subjects (P < 0.001).

Conclusions: In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone.
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http://dx.doi.org/10.1002/oby.20263DOI Listing
January 2013

Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism.

Atherosclerosis 2011 Oct 23;218(2):416-22. Epub 2011 Jul 23.

Department of Medicine, Universidad de Córdoba, Córdoba, Spain.

Objective: To investigate whether seven common single nucleotide polymorphisms (SNPs) at the lipoprotein lipase (LPL) locus interact with total plasma fatty acids to modulate plasma lipid metabolism in metabolic syndrome (MetS) patients.

Methods: Plasma fatty acid composition, plasma lipid concentrations and LPL SNPs were determined in 452 subjects with the MetS in the European LIPGENE human study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX Study.

Results: Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P<0.001), and these findings showed a similar, non-significant trend in LIPGENE cohort. In this last cohort, we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P<0.05). Moreover, subjects carrying the minor allele for rs328 SNP and with a low level of n-6 PUFA displayed higher nonesterified fatty acid (NEFA) plasma concentrations as compared with homozygous for the major allele (P=0.034). Interestingly, the n-6 PUFA-dependent associations between those SNPs and TG metabolism were also replicated in subjects without MetS from the SU.VI.MAX cohort.

Conclusion: Two genetic variations at the LPL gene (rs328 and rs1059611) influence plasma lipid concentrations and interact with plasma n-6 PUFA to modulate lipid metabolism. The knowledge of new genetic factors together with the understanding of these gene-nutrient interactions could help to a better knowledge of the pathogenesis in the MetS.
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http://dx.doi.org/10.1016/j.atherosclerosis.2011.07.092DOI Listing
October 2011

Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome.

PLoS One 2011 6;6(6):e20555. Epub 2011 Jun 6.

Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain.

Unlabelled: Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk.

Objective: To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects.

Design: Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.

Results: Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.

Conclusions: We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.

Trial Registration: ClinicalTrials.gov NCT00429195.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020555PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108949PMC
September 2011

Calpain-10 interacts with plasma saturated fatty acid concentrations to influence insulin resistance in individuals with the metabolic syndrome.

Am J Clin Nutr 2011 May 9;93(5):1136-41. Epub 2011 Mar 9.

Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion, Instituto de Salud Carlos III, Córdoba, Spain.

Background: Calpain-10 protein (intracellular Ca(2+)-dependent cysteine protease) may play a role in glucose metabolism, pancreatic β cell function, and regulation of thermogenesis. Several CAPN10 polymorphic sites have been studied for their potential use as risk markers for type 2 diabetes and the metabolic syndrome (MetS). Fatty acids are key metabolic regulators that may interact with genetic factors and influence glucose metabolism.

Objective: The objective was to examine whether the genetic variability at the CAPN10 gene locus is associated with the degree of insulin resistance and plasma fatty acid concentrations in subjects with MetS.

Design: The insulin sensitivity index, glucose effectiveness, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], insulin secretion (disposition index, acute insulin response, and HOMA of β cell function), plasma fatty acid composition, and 5 CAPN10 single nucleotide polymorphisms (SNPs) were determined in a cross-sectional analysis of 452 subjects with MetS participating in the LIPGENE dietary intervention cohort.

Results: The rs2953171 SNP interacted with plasma total saturated fatty acid (SFA) concentrations, which were significantly associated with insulin sensitivity (P < 0.031 for fasting insulin, P < 0.028 for HOMA-IR, and P < 0.012 for glucose effectiveness). The G/G genotype was associated with lower fasting insulin concentrations, lower HOMA-IR, and higher glucose effectiveness in subjects with low SFA concentrations (below the median) than in subjects with the minor A allele (G/A and A/A). In contrast, subjects with the G/G allele with the highest SFA concentrations (above the median) had higher fasting insulin and HOMA-IR values and lower glucose effectiveness than did subjects with the A allele.

Conclusion: The rs2953171 polymorphism at the CAPN10 gene locus may influence insulin sensitivity by interacting with the plasma fatty acid composition in subjects with MetS. This trial was registered at clinicaltrials.gov as NCT00429195.
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http://dx.doi.org/10.3945/ajcn.110.010512DOI Listing
May 2011

A low-fat, high-complex carbohydrate diet supplemented with long-chain (n-3) fatty acids alters the postprandial lipoprotein profile in patients with metabolic syndrome.

J Nutr 2010 Sep 14;140(9):1595-601. Epub 2010 Jul 14.

Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain.

Dietary fat intake plays a critical role in the development of metabolic syndrome (MetS). This study addressed the hypothesis that dietary fat quantity and quality may differentially modulate postprandial lipoprotein metabolism in MetS patients. A multi-center, parallel, randomized, controlled trial conducted within the LIPGENE study randomly assigned MetS patients to 1 of 4 diets: high-SFA [HSFA; 38% energy (E) from fat, 16% E as SFA], high-monounsaturated fatty acid [HMUFA; 38% E from fat, 20% E as MUFA], and 2 low-fat, high-complex carbohydrate [LFHCC; 28% E from fat] diets supplemented with 1.24 g/d of long-chain (LC) (n-3) PUFA (ratio 1.4 eicosapentaenoic acid:1 docosahexaenoic acid) or placebo (1.24 g/d of high-oleic sunflower-seed oil) for 12 wk each. A fat challenge with the same fat composition as the diets was conducted pre- and postintervention. Postprandial total cholesterol, triglycerides (TG), apolipoprotein (apo) B, apo B-48, apo A-I, LDL-cholesterol, HDL-cholesterol and cholesterol, TG, retinyl palmitate, and apo B in TG-rich lipoproteins (TRL; large and small) were determined pre- and postintervention. Postintervention, postprandial TG (P < 0.001) and large TRL-TG (P = 0.009) clearance began earlier and was faster in the HMUFA group compared with the HSFA and LFHCC groups. The LFHCC (n-3) group had a lower postprandial TG concentration (P < 0.001) than the other diet groups. Consuming the LFHCC diet increased the TG (P = 0.04), large TRL-TG (P = 0.01), TRL-cholesterol (P < 0.001), TRL-retinyl palmitate (P = 0.001), and TRL-apo B (P = 0.002) area under the curve compared with preintervention values. In contrast, long-term ingestion of the LFHCC (n-3) diet did not augment postprandial TG and TRL metabolism. In conclusion, postprandial abnormalities associated with MetS can be attenuated with LFHCC (n-3) and HMUFA diets. The adverse postprandial TG-raising effects of long-term LFHCC diets may be avoided by concomitant LC (n-3) PUFA supplementation to weight-stable MetS patients.
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http://dx.doi.org/10.3945/jn.109.120816DOI Listing
September 2010

[The role of connexin 43 in preconditioning. Impact on mitochondrial function].

Kardiol Pol 2010 Jan;68(1):91-6

Zakład Biochemii Klinicznej, Katedra Biochemii Klinicznej, Uniwersytet Jagielloński Collegium Medicum, 31-501 Kraków.

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January 2010

[Variants of adiponectin gene as risk factors for the metabolic syndrome].

Przegl Lek 2009 ;66(5):257-62

Zakład Biochemii Klinicznej, Collegium Medicum, Uniwersytet Jagielloński, Kraków.

Adiponectin, a protein secreted by adipose tissue but present at low levels in obesity, is now widely recognized as a key determinant of insulin sensitivity and of protection against obesity-associated metabolic syndrome. The adiponectin gene is very polymorphic and several of its variants contribute to adiponectin level, function and are associated with metabolic syndrome phenotypes. The results differ ethnically. The association of identified variants with obesity and its consequences, type 2 diabetes and cardiovascular disease is reviewed. This data may enable patients at greater risk of the adverse effects of obesity to be identified and, as such, benefit from more targeted therapy and prevention.
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October 2009

The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary LDL phenotype transformation - insights from the LIPGENE study.

Clin Nutr 2009 Oct 28;28(5):510-5. Epub 2009 May 28.

Dept. Clinical Biochemistry, Jagiellonian University School of Medicine, Krakow, Poland.

Background & Aims: LDL phenotype B is associated with obesity, insulin resistance, hypertriglyceridemia and oxidative stress. The effect of plasma n-3/n-6 PUFA ratio on LDL phenotype transformation was investigated.

Methods: Patients with metabolic syndrome (n=99) received one of four isocaloric diets: (A) High-fat (38% energy) SFA-rich diet (HSFA); (B) High-fat (38% energy), MUFA-rich diet (HMUFA); (C), low-fat (LF) (28% energy), high-complex carbohydrate diet with 1.24g/d oleic sunflower oil (LFHCC) and (D): low-fat (28% energy), high-complex carbohydrate diet, with 1.24g/d LC n-3 PUFA (LFHCC n-3) for 12 weeks. Analysis of plasma lipid profile and LDL phenotype was done pre- and post-interventions.

Results: Post-dietary change of LDL density was a main effect observed in all groups. LFHCC n-3 and HFMUFA diets resulted in favorable alteration of LDL phenotype from B to A and decreased LDL density. In contrast, increased LDL density was observed in HSFA and LFHCC groups. The plasma pre-n3/n6 PUFA, Apo E change and pre-Apo CIII/CII ratios explained in 65% the post-dietary change of LDL density in diet LFHCC n-3 consumers.

Conclusions: Study demonstrates efficacy of dietary n-3 PUFA to modify pro-atherogenic to less atherogenic LDL phenotype in patients with metabolic syndrome. Study identifier at ClinicalTrials.gov was NCT00429195.
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http://dx.doi.org/10.1016/j.clnu.2009.04.016DOI Listing
October 2009

Variants of the adiponectin gene and type 2 diabetes in a Polish population.

Acta Diabetol 2009 Dec 28;46(4):317-22. Epub 2009 Jan 28.

Department of Metabolic Diseases, Medical College, Jagiellonian University, 15 Kopernika Street, 31-501, Kraków, Poland.

Several association studies of type 2 diabetes mellitus (T2DM) and adiponectin gene polymorphisms have been reported with conflicting results. Our aim was to search for the association of three polymorphisms (-11.391G>A, +45T>G, and +276G>T) in the adiponectin gene with T2DM and prediabetic quantitative traits in Polish Caucasians. The study groups comprised 495 unrelated T2DM cases and 435 controls. We compared the distribution of genotypes between study groups. In addition, genotype-quantitative trait analyses were also done in the controls. The study subjects were genotyped using the restriction fragment length polymorphism technique. The frequencies of the minor alleles were as follows: 10.6 versus 8.2% for -11.391G>A (p = 0.0722), 7.0 versus 8.0% for +45T>G (p = 0.48), and 15.5% in T2DM versus 19.8% in controls (p = 0.0145) for +276G>T, respectively. The difference for genotype distribution between the groups was statistically significant (p = 0.0247) for the +276G>T variant: 71.31 versus 62.99%, 26.46 versus 34.48% and 2.22 versus 2.53%, respectively, for GG, GT and TT. In quantitative traits analysis, the T allele of +276G>T was associated (p < 0.05) with lower insulin resistance (HOMA-IR, fasting insulin) among controls. Additionally, the A allele at position -11.391 was associated (p < 0.05) with higher insulin resistance (HOMA-IR, fasting insulin). In multiple regression analysis, all identified association remained significant after the inclusion in the model of gender, BMI and age. In addition, in this model, -11.391G>A and +276G>T were independently associated with T2DM. Finally, we conclude that the adiponectin gene polymorphisms are associated with T2DM and prediabetic quantitative traits in Polish Caucasians.
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http://dx.doi.org/10.1007/s00592-008-0091-2DOI Listing
December 2009

Gene polymorphisms predisposing to cardiac hypertrophy in patients with cardiac syndrome X.

Folia Med Cracov 2007 ;48(1-4):57-69

Colegium Medicum Uniwersytetu Jagiellońskiego, Kraków.

Polymorphisms of the angiotensin-converting enzyme gene and endothelial nitric oxide synthase gene have been suggested to be associated with left ventricular hypertrophy. The aim of our study was to asses the association between above polymorphisms and left ventricular hypertrophy in patients with cardiac syndrome X. The presence of allele 4 of eNOS VNTR polymorphism could predispose to cardiac hypertrophy. The pathological course of postprandial lipemia in patients with CSX may add to the understanding of the CSX pathology.
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February 2009

LIPGENE food-exchange model for alteration of dietary fat quantity and quality in free-living participants from eight European countries.

Br J Nutr 2009 Mar 5;101(5):750-9. Epub 2008 Aug 5.

Department of Food Biosciences, University of Reading, Reading, UK.

Controlled human intervention trials are required to confirm the hypothesis that dietary fat quality may influence insulin action. The aim was to develop a food-exchange model, suitable for use in free-living volunteers, to investigate the effects of four experimental diets distinct in fat quantity and quality: high SFA (HSFA); high MUFA (HMUFA) and two low-fat (LF) diets, one supplemented with 1.24 g EPA and DHA/d (LFn-3). A theoretical food-exchange model was developed. The average quantity of exchangeable fat was calculated as the sum of fat provided by added fats (spreads and oils), milk, cheese, biscuits, cakes, buns and pastries using data from the National Diet and Nutrition Survey of UK adults. Most of the exchangeable fat was replaced by specifically designed study foods. Also critical to the model was the use of carbohydrate exchanges to ensure the diets were isoenergetic. Volunteers from eight centres across Europe completed the dietary intervention. Results indicated that compositional targets were largely achieved with significant differences in fat quantity between the high-fat diets (39.9 (sem 0.6) and 38.9 (sem 0.51) percentage energy (%E) from fat for the HSFA and HMUFA diets respectively) and the low-fat diets (29.6 (sem 0.6) and 29.1 (sem 0.5) %E from fat for the LF and LFn-3 diets respectively) and fat quality (17.5 (sem 0.3) and 10.4 (sem 0.2) %E from SFA and 12.7 (sem 0.3) and 18.7 (sem 0.4) %E MUFA for the HSFA and HMUFA diets respectively). In conclusion, a robust, flexible food-exchange model was developed and implemented successfully in the LIPGENE dietary intervention trial.
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http://dx.doi.org/10.1017/S0007114508039962DOI Listing
March 2009

[Leptin to adiponectin ratio, as an index of insulin resistance and atherosclerosis development].

Przegl Lek 2008 ;65(12):844-9

Zakład Biochemii Kliniicznej, Collegium Medicum UJ. Kraków.

Obesity is an effect of interaction of genetic and environmental factors. It leads to development of serious complications, like insulin resistance, diabetes type 2, arterial hypertension and atherosclerosis. The adipose tissue is a place where many adipokines, mainly leptin and adiponectin, are produced and released. Adiponectin, which blood level is decreased in obesity is considered to have antidiabetic and antiatherogenic effect. While leptin, which blood level is increased in obesity, is associated with regulation of appetite, energy expenditure, lipids and carbohydrates metabolism, cellular differentiation and puberty. The aim of this research was estimation of leptin to adiponectin ratio (Lep/AdipoR) in the blood of patients who came from obese families. The study was carried out on 80 patients (43 female and 37 male). The antropometric examination with proportional contents of adipose tissue, oral glucose tolerance test (OGTT) and oral postprandial lipaemia test (OPLT) were performed. The fasting level of leptin (Elisa), adiponectin (Elisa) and von Willebrand factor (Elisa) lipidogram were performed. During OGTT blood was sampled in intervals of 30 minutes up to 2 hours, to measure glucose and insulin concentration. In fasting state and then every 2 hours after consumption of a high-fat meal (OPLT), (0, 2 hours, 4 hours, 6 hours, and 8 hours) blood was sampled for: trigliceride, glucose, free fatty acids and insulin concentration. The insulin resistance ratio (HOMA-IR) was calculated for each patient according to the formula: [insulin (mU/ml) x glucose (mmol/l)]/22.5. Adiponectin blood level was higher in the examined women than in men. It (regardless to the sex) was decreased with decrease of body mass index (BMI). Blood level of leptin (also higher in women) was positively corelated with BMI. In the group of patients with low level of adiponectin in serum (below 5mg/ml in men and 10 mg/ml in women) the highest con- centration of glucose and insulin in successive time points of OGTT and the highest HOMA-IR value (4.79 in men and 4.38 in women) were observed. In patients with high level of leptin in serum (over 20 ng/ml), the highest concentration of insulin, especially in 2 hours of the test (101.75 micromol/ l), and the highest HOMA-IR value (4.30 during OPLT ) were found. The Lep/AdipoR in the blood was significantly higher in obese patients in comparison to people with normal BMI. Lep/AdipoR had high correlation factor with BMI (r = 0.6267, p < 0.001), with HOMA-IR (r = 0.5080, p < 0.001), with fasting insulin concentration (r = 0.5444, p < 0.001), and in 2 hour of OPLT (r = 0.5552, p < 0.001). ROC analysis (Receiver or Relative Operating Characteristic) showed that with reference to obesity Lep/AdipoR had the highest discriminatory value. The estimation of Lep/AdipoR can be used as additional index in evaluation of obesity complications such as insulin resistance and endothelial dysfunction.
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June 2009

Evaluation of genetic predisposition to insulin resistance by nutrient-induced insulin output ratio (NIOR).

Clin Chem Lab Med 2007 ;45(9):1124-32

Department of Clinical Biochemistry, The Jagiellonian University, Medical College, Krakow, Poland.

Background: New tools to identify genotype-phenotype interactions need to be described and implemented. The aim of this study was to identify correlation between the risk originating from gene variation and diet-dependent development of insulin resistance.

Methods: Insulin output in terms of area under the curve after an oral glucose tolerance test (AUC Ins OGTT) and lipid tolerance tests (AUC Ins OLTT) were measured in 167 overweight/obese patients. Estimation of the 18 common gene polymorphisms for obesity risk and standard phenotyping were performed.

Results: Insulin output (AUC Ins OGTT) correlated strongly between both insulin treatments across the whole group. However, within the genotype sub-groups, correlation was lower or did not exist. Using a nutrient-induced insulin output ratio (NIOR), calculated as AUC Ins OLTT/AUC Ins OGTT, values ranged from 0.42 to 5.83 and correlated significantly with body mass index (BMI) and leptin, but not with age, gender, waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) or plasma adiponectin. High NIOR was found in a subgroup of carriers of rare allelic variants of genes characteristic for poorer tolerance to lipids in the diet. Low NIOR values were found within a sub-group with rare genetic variants regulating carbohydrate metabolism. Thus, the new insulin index NIOR may distinguish gene variant carriers into groups of glucose- or lipid-sensitive phenotypes.

Conclusions: We suggest that the OLTT/OGTT insulin output ratio (NIOR) may be predictive for identifying individuals who are phenotypically susceptible to insulin resistance in response to high fat or carbohydrate in their habitual diet.
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http://dx.doi.org/10.1515/CCLM.2007.142DOI Listing
January 2008

Genetic Aspects of Obesity.

EJIFCC 2006 Dec 1;17(4):142-158. Epub 2006 Dec 1.

Department of Clinical Biochemistry, The Jagiellonian University Medical College Kopernika 15a 31 501 Kraków Poland tel: + 48 12 421 40 06fax: + 48 12 421 40 73.

The paper reviews recent problems in understanding of the genetic basis and gene/gene, as well as gene/environment interaction in the development of obesity and its complications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891777PMC
December 2006

[Nutrigenomics--about genetics and nutrition].

Przegl Lek 2005 ;62(4):245-52

Zakład Biochemii Klinicznej, Collegium Medicum Uniwersytet Jagielloński, Kraków.

Nutrigenomics is a promising multidisciplinary field that focus on studying the interactions between nutritional factors, genetic factors and health outcomes. Its goal is to achieve more efficient individual dietary intervention strategies aimed at preventing disease, improving quality of life and achieving healthy aging. Somehow, nutrigenomics has been used for decades in certain rare monogenic diseases such as phenylketonuria. It has the potential to provide a basis for personalized dietary recommendations based on the individual's genetic makeup in order to prevent common multifactorial disorders (such as metabolic syndrome) decades before their clinical manifestation. Preliminary results regarding gene-diet interactions in many diseases are for the most part inconclusive because of the limitations of current designs. Success in this area will require the integration of various disciplines (e.g. biotechnology, medicine, biology, economics) and will require investigators to work on ethnic groups. This knowledge should lead to successful dietary recommendations partly based on genetic factors that may help to reduce disease risk more efficiently than the current universal recommendations based mainly on epidemiological studies. We discuss nutrigenomic issues and show examples for this new, with a wide research area, field of science.
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December 2005

[Chlamydia pneumoniae and cardiovascular diseases].

Przegl Lek 2004 ;61(3):165-9

II Klinika Kardiologii, Instytutu Kardiologii, Collegium Medicum, Uniwersytetu Jagiellońskiego w Krakowie.

The theories formulated to explain atherogenesis evolved from vessel wall lipid to endothelial dysfunction with vascular wall remodelling. Chlamydia pneumoniae has been demonstrated to play an important role in the development of inflammatory and immunological process and can initiate atherogenesis. This pathogen is found in atherosclerotic plaques, which can induce complex activation of local inflammatory and immunological events and lead to the development of unstable plaque, vascular remodelling and vessel lumen constriction.
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December 2004