Bogna Grygiel-Górniak

Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review

Peroxisome proliferator-activated receptors are expressed in many tissues, including adipocytes, hepatocytes, muscles and endothelial cells; however, the affinity depends on the isoform of PPAR, and different distribution and expression profiles, which ultimately lead to different clinical outcomes. Because they play an important role in lipid and glucose homeostasis, they are called lipid and insulin sensors. Their actions are limited to specific tissue types and thus, reveal a characteristic influence on target cells. PPARα mainly influences fatty acid metabolism and its activation lowers lipid levels, while PPARγ is mostly involved in the regulation of the adipogenesis, energy balance, and lipid biosynthesis. PPARβ/δ participates in fatty acid oxidation, mostly in skeletal and cardiac muscles, but it also regulates blood glucose and cholesterol levels. Many natural and synthetic ligands influence the expression of these receptors. Synthetic ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARγ agonists). New generation drugs - PPARα/γ dual agonists - reveal hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action while the overexpression of PPARβ/δ prevents the development of obesity and reduces lipid accumulation in cardiac cells, even during a high-fat diet. Precise data on the expression and function of natural PPAR agonists on glucose and lipid metabolism are still missing, mostly because the same ligand influences several receptors and a number of reports have provided conflicting results. To date, we know that PPARs have the capability to accommodate and bind a variety of natural and synthetic lipophilic acids, such as essential fatty acids, eicosanoids, phytanic acid and palmitoylethanolamide. A current understanding of the effects of PPARs, their molecular mechanisms and the role of these receptors in nutrition and therapeutic treatment are delineated in this paper.

Oxidative Damage and Antioxidative Therapy in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder of unknown etiology. This disease is characterized by a large variety of clinical patterns, which include the fibrosis of skin and visceral organs causing a variety of clinical manifestations. Genetic and environmental factors participate in the etiology of this disease; however, recently many studies underline the oxidative background influencing the course and complications of this disease. Reactive oxygen species (ROS) synthesized in SSc can mediate extra- and intracellular oxidative processes affecting endothelial cells and fibroblasts. The estimation of prooxidative markers in the pathogenesis of SSc can enable the identification of useful markers for disease activity and, thus, may help in planning appropriate therapy focusing on the fibrotic or vascular pattern. Recently, many attempts have been made to find antioxidative molecules (nutritional and pharmacological) reducing the prooxidant state in a variety of cells—mainly in endothelium and proliferating fibroblasts. This paper presents both the background of oxidative stress processes in systemic sclerosis mediated by different mechanisms and the evidence suggesting which of the dietary and pharmacological antioxidants can be used as therapeutic targets for this disease.

Dietary Habits and Nutritional Status of Female Adolescents from the Great Poland Region

Dietary Habits and Nutritional Status of Female Adolescents from the Great Poland Region The aim of this study was to assess the nutritional status and dietary habits among female adolescents. Four hundred seventy nine subjects aged from 17 to 18 years, from secondary schools of the Great Poland Region participated in the study. Anthropometric parameter measurements included those of body height and mass, skinfold thickness and circumferences of waist, hip and arm. The measurements served to calculate the percentage of fat mass and arm muscle area. Nutritional questionnaires were used to estimate the frequency and intake of selected food products. Mean values of body height and mass were approximately in the 50th percentile. However, 13.7% of females were underweight, 7.7% were overweight and 1.2% were obese. Cluster analysis resulted in 3 clusters, of which the second one showed the most detrimental nutritional habits. This cluster was characterised by the lowest intake of dairy products, fruits and vegetables, fish, meat and also by frequent long breaks between meals (longer than 5 hours). Improper nutritional behavior is a frequent finding in female adolescents, in Poland. Nevertheless, overweight and obesity are not more common than in other countries. Studies in this area should be continued and extended.

Association of PPAR-γ2 and β3-AR Polymorphisms With Postmenopausal Hypertension.

The aim of this study was to test the association of peroxisome proliferator‐activated receptor (PPAR‐γ2) (Pro12Ala, C1431T) and β3‐AR (Trp64Arg) polymorphisms with metabolic, nutritional, and blood pressure parameters in 271 postmenopausal women (151 hypertensive and 120 normotensive controls). The TaqMan genotyping assay and restriction fragment length polymorphism methods were used to determine the distributions of selected alleles and genotype frequencies. Nutritional status was determined by a bioimpedance method and dietary habits were assessed via 7‐day dietary recall. The distribution of selected genotypes and allele frequencies did not differ between hypertensive women and normal controls after analysis by chi‐square test. The postmenopausal hypertensive women were older and had higher body fat mass, serum glucose, and triglyceride levels. The cluster analysis showed that the hypertensive group with Pro12Pro genotype had highest pulse pressure and mean arterial pressure values when compared with Pro12Ala patients. In the logistic regression analysis, blood glucose (Pro12Ala polymorphism) and energy intake (C1431Tand T1431T polymorphisms) determined hypertension.

The influence of endogenous and exogenous sex hormones on systemic lupus erythematosus in pre- and postmenopausal women

Systemic lupus erythematosus (SLE or lupus) is a chronic inflammatory disease that occurs mainly in women. Typically, symptoms appear within the first few years of adolescence, but currently an increase can be observed in the percentage of postmenopausal women with this condition. This is possibly due to the sophisticated treatment of the disease, which significantly improves the survival curve and prognosis. Genetic and environmental factors are involved in the development of SLE. Both regulation of the immune system and the activity of this disease are influenced by a variety of hormones, including: 17β-estradiol, testosterone, prolactin, progesterone and dehydroepiandrosterone (DHEA). Early menarche, menstrual cyclicity, the total number of years characterized by ovulatory cycles and early menopause are correlated with the development of SLE. Because of the health risks, attempts are increasingly being made to evaluate the impact of exogenous hormones (especially those applied exogenously) on the course of SLE. In particular, the role of estrogens is being highlighted, either endo- or exogenous, including oral contraceptives (OC), therapy used in the treatment of infertility, and hormonal replacement therapy (HRT). The purpose of this manuscript is the revision of the literature concerning the impact of both endo- and exogenous estrogens on the development of lupus, inducement of flares and any possible complications.

The gene-diet associations in postmenopausal women with newly diagnosed dyslipidemia

ObjectivesThe aim of this study was to determine the relationship between polymorphisms of peroxisome proliferator activated receptor - PPAR gamma-2 (Pro12Ala, C1431T) and beta 3-adrenergic receptor - ADRB3 (Trp64Arg) and dietary habits in a group of postmenopausal women who were not under hypolipidemic treatment.DesignGenetic, nutritional and anthropometric parameters were measured in 213 dyslipidemic (LDL ≥115 mg/dL) and 58 normolipidemic (LDL<115) postmenopausal women. The PCR-RFLP method were used to determine the distributions of selected alleles and genotype frequencies. Dietary intake of basic components and fatty acids was obtained from a 7-day weighed food record and the bio-impedance method was used to determine nutritional status.ResultsNearly 79% of analyzed women were in the firsttime-diagnosed dyslipidemic state. The dyslipidemic subjects were characterized with higher intake of energy, fat, and saturated fatty acids (SFA). The analysis of the same polymorphisms showed association at the P value <0.05 with nutrients (fat, SFA, and polyunsaturated fatty acid - PUFA and saccharose) and elevated LDL level. Higher PUFA intake in a group of women with the protective Ala12/X polymorphism did not increase the risk of dyslipidemia even though they were characterized by visceral distribution of fat. The Arg64/X polymorphism and higher intake of energy, fat, and arachidic acid intake (C20:0) were associated with dyslipidemic state.ConclusionBoth nutritional and genetic factors are related to lipid profile. The identification of gene-diet associations is likely to provide useful information about the etiology of postmenopausal dyslipidemia and help in effective treatment.

Impact of the PPAR gamma-2 gene polymorphisms on the metabolic state of postmenopausal women

The relationship Pro12Ala (rs1801282) and C1431T (rs3856806) polymorphisms of PPAR gamma-2 with glucose and lipid metabolism is not clear after menopause. We investigated the impact of the Pro12Ala and C1431T silent substitution in the 6th exon in PPAR gamma-2 gene on nutritional and metabolic status in 271 postmenopausal women (122 lean and 149 obese). The general linear model (GLM) approach to the two-way analysis of variance (ANOVA) was used to infer the interactions between the analysed genotypes. The frequency of the Pro-T haplotype was higher in obese than in lean women (p<0.0349). In the analysed GLM models according to obesity status, the C1431C genotype was related to a lower glucose concentration (β=−0.2103) in lean women, and to higher folliculotropic hormone FSH levels (β=0.1985) and lower waist circumferences (β=−0.1511) in obese women. The influence of C1431C was present regardless of the occurrence of the Pro12Ala polymorphism. The co-existence of the C1431C and Pro12Pro genotypes was related to lower values for triceps skinfold thickness compared those for the T1241/X and Ala12/X polymorphisms (β=−0.1425). The presence of C1431C decreased the differences between triceps values that were determined by Pro or Ala allele. In conclusion, C1431T polymorphism seems to have a more essential influence on anthropometric and biochemical parameters than is the case with Pro12Ala polymorphism.

Fatigue and interleukin-6 – a multi-faceted relationship

Many connective tissue diseases are characterized by fatigue, which is described in the literature as prostration, weakness, lassitude or asthenia. In many other diseases (autoimmune, neurologic or metabolic) fatigue impinges on daily activities and thus influences the quality of life. Different molecular backgrounds are involved in the development of fatigue. Not only does the immunosuppressive treatment of autoimmune diseases reduce fatigue, but also selective nutritional components may have an effect on secretion of cytokines which are responsible for development of the sensation of tiredness (e.g. secretion of interleukin-6). The beneficial influence of selected food components (such as polyunsaturated omega-3 fatty acids, nutritional antioxidants or adequate fat intake with the diet) on proinflammatory cytokine secretion has been demonstrated in many studies. In this review, the biochemical, neurological and nutritional aspects of fatigue in autoimmune diseases are underlined.

[Vitamin D--a new look in medicine and rheumatology].

The research of the last decade pointed to the importance of vitamin D not only in bone metabolic processes, but also in immunologic and anticarcinogenic processes. Thus, its common insufficiency is related to serious health consequences--e.g. increased mortality and morbidity caused by autoimmune and cancer diseases. The modification of the range of values of vitamin D serum concentration and revision of its nutritional and pharmacological recommendations are suggested nowadays. Moreover, the discovery of the vitamin D receptor (VDR) enables us to understand its influence on other organs. To date the new properties of vitamin D are elucidated in the literature showing its preventive effect and possible application in supportive treatment of many diseases.

Lipid Profile and Non-Cholesterol Sterols in Obese Women's Serum after Supplementing with Plant Stanol Ester

Background: The aim of this study was to assess the influence of increased plant stanol ester intake on lipid profile and serum ratio of non-cholesterol sterols to cholesterol in obese women (50 years of age) with dyslipidemia. Methods: 90 females were assigned into 2 treatment groups: For a period of 4 weeks, group 1 was receiving a yoghurt, enriched with 2 g of plant stanol ester (PS group), and group 2 was receiving a yoghurt drink without extra stanols. Anthropometric measurements included body height and weight. Lipid profile was determined by commercially available enzymatic methods. Serum non-cholesterol sterols and stanols concentrations were quantitated by gas chromatography. The study was single-blind and placebo-controlled. Results: The yoghurt drink enriched with plant stanol ester significantly reduced serum total cholesterol, LDL cholesterol, and non-HDL cholesterol levels (p < 0.05). No changes were observed in HDL cholesterol and triacylglycerol levels. The highest drop of LDL cholesterol was noted in the upper quartile of total cholesterol concentrations. In the PS group the statistically significant (p < 0.0001) changes were also observed in serum ratios of non-cholesterol sterols to cholesterol: campesterol, sitosterol, sitostanol, and avenasterol. Conclusion: Plant stanol esters influence the concentration of total cholesterol, particularly LDL cholesterol. This effect seems to be related to the reduced dietary cholesterol absorption.