Publications by authors named "Nathalie Meier-Allard"

9 Publications

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Obesity Affects HDL Metabolism, Composition and Subclass Distribution.

Biomedicines 2021 Feb 27;9(3). Epub 2021 Feb 27.

Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight ( = 26), overweight ( = 22), and obese ( = 20) women.

Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women.

Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.
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http://dx.doi.org/10.3390/biomedicines9030242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997277PMC
February 2021

Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption.

Nutrients 2020 Nov 30;12(12). Epub 2020 Nov 30.

Division of Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz, Heinrichstrasse 31a, A-8010 Graz, Austria.

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal-Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption ( < 0.004 and < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal-Wallis test AUCs demonstrated a significant difference between all three groups ( = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.
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http://dx.doi.org/10.3390/nu12123690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761160PMC
November 2020

Effects of a plant-based fatty acid supplement and a powdered fruit, vegetable and berry juice concentrate on omega-3-indices and serum micronutrient concentrations in healthy subjects.

Int J Food Sci Nutr 2020 Sep 17;71(6):769-780. Epub 2020 Feb 17.

Green Beat - Institute of Nutrient Research and Sport Nutrition, Graz, Austria.

The major aim of this controlled, randomised, open-labelled, parallel-grouped, clinical trial was to investigate whether supplementation with different dosages of omega-3 fatty acids (0.5 g/d and 1 g/d) from a plant-based fatty acid supplement affected omega-3-indices (O3I) in well-nourished, healthy people. In addition, the combined ingestion of the plant-based fatty acid supplement, together with an encapsulated fruit, vegetable and berry (FVB) juice powder concentrate, was applied in order to observe the absorption of certain micronutrients and to examine some aspects related to the safe consumption of the products. The data demonstrate that the intake of only 0.5 g/day of omega-3 fatty acids from of a vegan supplement was able to increase the O3I significantly after 8 and 16 weeks. The combined ingestion with the FVB supplement concurrently increased serum concentrations of specific vitamins and carotenoids without effects on hepatic, kidney and thyroid function or changes in blood lipids.
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http://dx.doi.org/10.1080/09637486.2020.1725960DOI Listing
September 2020

An encapsulated fruit, vegetable and berry juice powder concentrate increases plasma values of specific carotenoids and vitamins.

Int J Vitam Nutr Res 2021 Jan 15;91(1-2):77-86. Epub 2019 Nov 15.

Green Beat - Institute of Nutrient Research and Sport Nutrition, Graz, Austria.

Vitamins and carotenoids are organic compounds that are important for vital functions of the human organism. Since the human body is not able to synthesize most of these micronutrients, they need to be supplied by the intake of food or supplements. The aim of this study was to analyze whether a whole food based, encapsulated fruit, berry, and vegetable juice powder concentrate provides bioavailable carotenoids and vitamins A (all-trans retinol), E and C. Eighteen healthy subjects received 6 capsules a day for 8 weeks, which provided 2.91 mg β-carotene, 490 μg vitamin A, 18.7 mg vitamin E, 159 mg vitamin C, 6.1 mg lutein and 1 mg lycopene. Plasma concentrations of several carotenoids and vitamins before and after supplementation were measured. After 8 weeks of supplementation, the plasma concentration of the following carotenoids increased significantly: α-carotene increased from 59.6 ± 22.4 nmol/L to 85.7 ± 24.2 nmol/L (p = 0.002), β-cryptoxanthin from 106.7 ± 39.8 nmol/L to 151.9 ± 57.9 nmol/L (p = 0.017), and lycopene from 1.2 ± 0.5 μmol/L to 1.7 ± 0.5 μmol/L (p = 0.005). Significant increases were also observed for plasma concentrations of vitamin C from 70 ± 20 μmol/L to 90 ± 10 μmol/L (p < 0.001), all-trans retinol from 1.99 ± 0.24 μmol/L to 2.30 ± 0.66 μmol/L (p = 0.015), and α-tocopherol from 27 ± 6 μmol/L to 32 ± 6 μmol/L (p = 0.008). For those micronutrients with accepted plasma reference ranges, all observed increases levelled off around the upper limit of the individual reference range. The data demonstrate that the investigated supplement is able to increase plasma concentrations of certain carotenoids and vitamins of healthy subjects within 8 weeks.
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http://dx.doi.org/10.1024/0300-9831/a000609DOI Listing
January 2021

Prazosin induced lysosomal tubulation interferes with cytokinesis and the endocytic sorting of the tumour antigen CD98hc.

Biochim Biophys Acta Mol Cell Res 2018 09 15;1865(9):1211-1229. Epub 2018 Jun 15.

Research Unit Functional Proteomics and Metabolic Pathways, Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria; Omics Center Graz, BioTechMed-Graz, Stiftingtalstrasse 24, 8010 Graz, Austria.

The quinazoline based drug prazosin (PRZ) is a potent inducer of apoptosis in human cancer cells. We recently reported that PRZ enters cells via endocytosis and induces tubulation of the endolysosomal system. In a proteomics approach aimed at identifying potential membrane proteins with binding affinity to quinazolines, we detected the oncoprotein CD98hc. We confirmed shuttling of CD98hc towards lysosomes and upregulation of CD98hc expression in PRZ treated cells. Gene knockout (KO) experiments revealed that endocytosis of PRZ still occurs in the absence of CD98hc - suggesting that PRZ does not enter the cell via CD98hc but misroutes the protein towards tubular lysosomes. Lysosomal tubulation interfered with completion of cytokinesis and provoked endoreplication. CD98hc KO cells showed reduced endoreplication capacity and lower sensitivity towards PRZ induced apoptosis than wild type cells. Thus, loss of CD98hc does not affect endocytosis of PRZ and lysosomal tubulation, but the ability for endoreplication and survival of cells. Furthermore, we found that glutamine, lysomototropic agents - namely chloroquine and NHCl - as well as inhibition of v-ATPase, interfere with the intracellular transport of CD98hc. In summary, our study further emphasizes lysosomes as target organelles to inhibit proliferation and to induce cell death in cancer. Most importantly, we demonstrate for the first time that the intracellular trafficking of CD98hc can be modulated by small molecules. Since CD98hc is considered as a potential drug target in several types of human malignancies, our study possesses translational significance suggesting, that old drugs are able to act on a novel target.
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http://dx.doi.org/10.1016/j.bbamcr.2018.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070144PMC
September 2018

Endoplasmic reticulum stress in bipolar disorder? - BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood.

Psychoneuroendocrinology 2018 09 21;95:113-119. Epub 2018 May 21.

Institute of Pathophysiology and Immunology, Medical University of Graz, Heinrichstrasse 31A, 8010 Graz, Austria.

Background: Endoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls.

Methods: RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR. Atypical splicing of XBP1 mRNA was measured by semi-quantitative RT-PCR, gel-electrophoresis and densitometry. ANCOVAs with the covariates age, BMI, sex, lithium and anticonvulsants intake were used with SPSS. Bonferroni correction was used to correct for multiple testing (adjusted p = 0.0083).

Results: BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η = 0.044) and the ratio spliced XBP1/ unspliced XBP1 did not differ between BD and controls (F(1/126) = 0.599, p = 0.441, Partial η = 0.005). Gene expression did not differ between euthymia, depression and mania.

Discussion: BiP gene expression was significantly higher in BD compared to controls. Total and unspliced XBP1 were significantly lower in BD than in the control group. Thus, both genes may be considered as putative trait markers. Nevertheless, XBP1 splicing itself did not differ between both groups.
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http://dx.doi.org/10.1016/j.psyneuen.2018.05.029DOI Listing
September 2018

Endoplasmic Reticulum Stress and Bipolar Disorder - Almost Forgotten Therapeutic Drug Targets in the Unfolded Protein Response Pathway Revisited.

CNS Neurol Disord Drug Targets 2016 ;15(4):403-13

Department of Psychiatry, Medical University of Graz, Auenbruggerplatz 31, A-8036 Graz, Austria.

Bipolar Disorder (BD) is characterized by recurring mood swings, which are not completely understood yet. So far, it is an accepted theory that multiple factors contribute to pathogenesis of BD according to the vulnerability-stressmodel. This model combines on the one hand biological predisposing vulnerability, and on the other hand several chronic and acute stressful negative events as underlying mechanisms of BD. Recently, ER (Endoplasmic Reticulum) stress reached the spotlight of BD research again. The expression of the chaperone BiP (syn. GRP78/glucose-regulated protein, 78kDa), which is highly expressed in the Endoplasmic Reticulum (ER), is upregulated by different kinds of mood stabilizers. These results implied that the ER, an organelle which is prone towards different kinds of cellular stress, might be involved in the pathophysiology of BD. This hypothesis was further strengthened by hypothesis driven genetic association studies, which showed significant association of BiP promotor polymorphisms with BD. Also other ER-stress associated genes like XBP1 (X-box binding protein 1) or GRP94 (glucose-regulated protein, 94kDa, synonym for heat shock protein HSP90B1) were recently linked to BD in hypothesis driven gene association studies. In addition to the proteins mentioned before, our review focuses on further UPR (Unfolded Protein Response) related proteins associated with BD and raises the hypothesis that ER-stress may represent a common interface between BD and obesity which is overrepresented in BD patients. Finally, members of the UPR pathway are discussed as putative targets for mood stabilizers.
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http://dx.doi.org/10.2174/1871527315666160321104613DOI Listing
December 2016

Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells.

Mol Med Rep 2015 Oct 7;12(4):5003-11. Epub 2015 Jul 7.

Department of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz A‑8010, Austria.

Medullary thyroid carcinoma (MTC) originates from the C‑cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC‑SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription‑quantitative polymerase chain reaction of nuclear factor‑κB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC‑bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC‑SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC‑mice, and no change in the expression of NEMO was detected in the treated MTC‑SK cells. The observation of early‑onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti‑apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC‑SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway.
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http://dx.doi.org/10.3892/mmr.2015.4053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581794PMC
October 2015

The anti-hypertensive drug prazosin induces apoptosis in the medullary thyroid carcinoma cell line TT.

Anticancer Res 2015 Jan;35(1):31-38

Institute of Pathophysiology and Immunology, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.

Background/aim: Medullary thyroid carcinoma (MTC) is a tumor associated with poor prognosis since it exhibits high resistance against conventional cancer therapy. Recent studies have shown that quinazolines exhibit a pro-apoptotic effect on malignant cells. The aim of the present study was to elucidate whether MTC cells are affected by quinazolines, in particular prazosin.

Materials And Methods: Proliferation, apoptosis and cell morphology of the MTC cell line TT were analyzed by WST-1 assay, caspase 3/7 activation tests and microscopy. Fibroblasts were used as control for non-malignant cells.

Results: Prazosin potently inhibited the growth of TT cells, induced apoptosis and caused vacuolization, as well as needle-like filopodia. Fibroblasts were affected by prazosin in the same way as MTC cells.

Conclusion: MTC cells are responsive to prazosin treatment similar to other malignancies. The fact that fibroblasts also respond to prazosin further highlights the importance to identify the unknown pro-apoptotic target of quinazolines.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290659PMC
January 2015