943 research outputs found
Transcriptomic analysis of Simpson Golabi Behmel Syndrome cells during differentiation exhibit BAT-like function
No full textHigh-throughput RNA sequencing of human Simpson-Golabi-Behmel syndrome cells (SGBS) was performed during the time-course of adipogenic differentiation at day 4 (D04), 6 (D06), 8 (D08), and 10 (D10) to characterize transcriptomic changes and to identify key patterns involved in adipogenesis and browning. In the comparisons, 932 and 384 overlapping transcripts were consistently up- and down-regulated, respectively. Combining the results of protein-protein interaction network analysis MCODE and CytoHubba, 55 up-regulated hub genes from four clusters and 9 down-regulated genes were identified. The up-regulated hub genes were mainly enriched in brown adipocyte differentiation, extracellular matrix organization, and valine, leucine, and isoleucine degradation. The enrichment of downregulated hub genes was related to NRF2 signalling and glutathione metabolism, indicating that oxidative stress also plays a role. Analysis of overlapping down-regulated genes, targets of transcription factors, revealed enrichment in the IL-18 signalling pathway, which is involved in browning process and extracellular matrix organization via actomyosin mechanics and integrin-extracellular matrix interactions. Finally, the comparison transcriptomic analysis with the gene signature reported by BATLAS and PROFAT web-based tools showed an increased percentage of the brown phenotype, confirming that differentiated SGBS cells at D06, D08, and D10 gradually acquire BAT-like function
Stellungnahme der Ernährungskommission der Deutschen Gesellschaft für Kinder- und Jugendmedizin zur Vermarktung von Beikostprodukten zur Flaschenfütterung
No full textBöhles HJ, Fusch C, Genzel-Boroviczény O, Henker J, Koletzko B , Kersting M, Lentze MJ, Maaser RG, Mihatsch W, Przyrembel H, Wabitsch
Can Nigella sativa oil control inflammation in human pre-adipocytes?
No full textObjectives: The fixed oil obtained from the seeds of Nigella
sativa L. (NS), also known as black cumin, is frequently used in the
Mediterranean area for its therapeutic properties. Pertaining literature
suggests that its anti-inflammatory, anti-oxidant and anticancer
activities is due to thymoquinone (TQ), a main component
of this oil, the bioactivity of which has been investigated mainly in
cancer models. Besides TQ, NS oil is rich of components (including
vitamins, amino acids, fatty acids, sterols, micro elements, etc.)
that can contribute to its biological activity.
We therefore aimed at evaluating TQ concentration in a Nigella
sativa oil extracted from seeds of cultivar produced in the
Marche region of Italy, and at determining if its content, antioxidant
properties and biological activity decay during storage. Cytotoxicity
and anti-inflammatory properties of NS oil were tested in
an in vitro model of low-grade inflammation of Simpson-Golabi-
Behmel syndrome (SGBS) human pre-adipocytes to assess if this
oil, or equal concentration of synthetic thymoquinone, could affect
the production of pro-inflammatory cytokines.
Methods: Fresh extracted oil (FEO) and old extracted oil
(OEO) were evaluated for their content in TQ by gas chromatography
coupled to flame ionization detection (GC-FID). Total Antioxidant
Activity (TAA), Oxygen Radical Absorbance Capacity
(ORAC), Luminol-amplified- and lucigenin-amplified-chemiluminescence
of FEO, OEO, TQ and medium from SGBS incubation
(MI) were analyzed for their scavenger capacity by spectrophotometric
and chemiluminescent assays. SGBS and monocytic leukemia
(THP1) cell lines where cultured as previously described by
Wabitsch and collaborators (Keuper et al., 2011). Cytotoxicity of
NS extracts (FEO, OEO) and solutions equivalent in terms synthetic
tymoquinone concentration (syntFEO) were tested by the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) assay for 24 h. Inflammation was induced in SGBS cells by
conditioning their culture medium with 15% of supernatant obtained
after THP1 differentiation with phorbol 12-myristate
13-acetate (PMA) for 48 h (Keuper et al., 2011). SGBS inflamed
cells were treated with FEO, OEO, syntFEO, solved in DMSO for
24 h. Cytokine production was assessed using Multi-Analyte
ELISArray Kits (Quiagen).
Results: the content of TQ in the NS oil from the Marche region
cultivar was higher compared with other NS oils produced in the
middle East and in other Mediterranean regions. The FEO contains33% more TQ than OEO, showing that storage affects its
overall quality. FEO and OEO showed similar cytotoxicity, but in
both cases lower than that of pure TQ. Pro-inflammatory cytokines
(e.g. IL-1alfa, IL-1beta, IL-6, IL-8 and GM-CSF) were differently
modulated by NS oils.
Conclusions: NS oil produced in the Italian Marche region has
a good content in TQ and a lower cytotoxicity than pure TQ. Its
capacity to counterbalance proinflammatory cytokine production
can be ascribed to the antioxidant properties of the other oil components
Lignan phytocomplexes extracted from legumes act as anti-inflammatory agents in a model of adipocyte metaflammation: antioxidant properties and nutriepigenomic effects
No full textBackground: Metaflammation, a state of metabolically driven inflammation also referred to as ‘low-grade’ inflammation, is a key contributor to the development of obesity complications such as type 2 diabetes and cardiovascular diseases. Among numerous phytochemicals, lignans are secondary metabolites whose biological properties have not been properly characterized yet. This study aims to investigate the effect on metaflammation of natural mix of lignans isolated from legumes and their synthetic equivalents and to evaluate the possible intermediating role of epigenetic on this process.
Methods: An in vitro model of inflamed adipocytes was used. Cytotoxicity of phytocomplexes was evaluated through MTT assay. Antioxidant properties were assessed by chemiluminescence assay. Gene expression of genes involved in inflammation (MCP1, IL6, IL1b, NFkB) or epigenetic regulation (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, HDAC3) were analyzed and global DNA methylation and H3 histone acetylation were measured.
Results: A protective effect of the selected mix of lignans against metaflammation in this model was measured. In particular, reduced level of inflammatory genes and altered expression of genes that regulate epigenetic pathways suggest a potential involvement of epigenetic mechanism as responsible for the measured antinflammatory effect. This was observed for both natural and synthetic mixtures, despite a limited antioxidant activity was measured in the second ones.
Conclusions: This study suggest that not only antioxidant activity but also nutriepigenomic effects could be responsible for the measured antinflammatory properties of the selected mixtures of lignans extracted from legumes. Further studies are needed to elucidate the underlying epigenetic molecular mechanisms
Lipodystrophy as a late effect after stem cell transplantation
No full textSurvivors of childhood cancer are at high risk of developing metabolic diseases in adulthood. Recently, several patients developing partial lipodystrophy following hematopoietic stem cell transplantation (HSCT) have been described. In this review, we summarize the cases described so far and discuss potential underlying mechanisms of the disease. The findings suggest that HSCT-associated lipodystrophies may be seen as a novel form of acquired lipodystrophy
Epidemiologie des Übergewichts und der Adipositas bei Kindern und Jugendlichen anhand von deutschen Schuleingangsdaten
No full textZusammenfassungIn Deutschland existiert das System der Schuleingangsuntersuchung. Im Rahmen dieser Untersuchung werden unter anderem Werte zum aktuellen Körpergewicht (kg) und zur aktuellen Körperhöhe (m) des Kindes erhoben. Der BMI (kg/m2) wird berechnet und mit Referenzwerten verglichen. Ein BMI größer dem 90. alters- und geschlechtsspezifischen Perzentil wird als Übergewicht und ein BMI größer dem 97. alters- und geschlechtsspezifischen Perzentil als Adipositas definiert. Eine Arbeitsgruppe bestehend aus Prof. Dr. med. Wabitsch, Dr. biol. hum. Moß, Dr. biol. hum. Klenk und PD Dr. rer. nat. Kromeyer-Hauschild hat in der Vergangenheit zu zwei Zeitpunkten die Daten der Schuleingangsuntersuchung in den einzelnen Bundesländern abgefragt (2004 und 2008). Zusätzlich wurde eine Literatursuche durchgeführt. Die Prävalenzraten für Übergewicht und Adipositas variierten zu beiden Zeitpunkten der Datenabfrage zwischen den Bundesländern. Im Vergleich zu 2004 zeigte sich im Jahr 2008 eine Reduktion der Prävalenzraten für Übergewicht und für Adipositas zum Zeitpunkt der Schuleingangsuntersuchung für die Mehrheit der Bundesländer.</jats:p
Therapeutic potential of the dual peroxisome proliferator activated receptor (PPAR)α/γ agonist aleglitazar in attenuating TNF-α-mediated inflammation and insulin resistance in human adipocytes
No full textSpare mitochondrial respiratory capacity permits human adipocytes to maintain ATP homeostasis under hypoglycemic conditions
No full textMitochondrial dysfunction in white adipose tissue plays a key role in the pathogenesis of type 2 diabetes. Emerging evidence specifically suggests that altered oxidative phosphorylation in adipocytes may have a relevant effect on systemic glucose homeostasis, requiring understanding of adipocyte bioenergetics. We analyzed energetic flux of an intact human adipocyte cell model by plate-based respirometry and extracellular acidification. During differentiation, we discovered that glycolytic ATP production was increasingly replaced by mitochondrial oxidative metabolism (from 20 to 60%). This observation was corroborated by simultaneous up-regulation of canonical mitochondrial gene programs, such as peroxisome proliferator-activated receptor coactivator (PGC1; 150-fold) and cytochrome c-1 (CytC; 3-fold). Mimicking diabetic phenotypes by exposure to various glucose levels (0, 5, and 25 mM) resulted in immediate adjustments of glycolytic and mitochondrial activity that aimed to maintain intracellular ATP. We conclude that ATP deficits by mitochondrial failure are compensated by glycolytic ATP production, resulting in inefficient conversion of glucose to cellular ATP. Metabolic inefficiency may enhance glucose uptake, therefore improving systemic glucose homeostasis. Notably, mature adipocytes developed a high spare respiratory capacity (increased by 6-fold) permitting rapid adaptation to metabolic changes. Spare respiratory capacity may also allow additional metabolic scope for energy dissipation, potentially offering new therapeutic targets for the treatment of metabolic disease.Keuper, M., Jastroch, M., Yi, C.-X., Fischer-Posovszky, P., Wabitsch, M., Tschop, M. H., Hofmann, S. M. Spare mitochondrial respiratory capacity permits human adipocytes to maintain ATP homeostasis under hypoglycemic condition
Metabolic risk-factor clustering estimation in children: to draw a line across pediatric metabolic syndrome.
No full textBACKGROUND: The diagnostic criteria of the metabolic syndrome (MS) have been applied in studies of obese adults to estimate the metabolic risk-associated with obesity, even though no general consensus exists concerning its definition and clinical value. We reviewed the current literature on the MS, focusing on those studies that used the MS diagnostic criteria to analyze children, and we observed extreme heterogeneity for the sets of variables and cutoff values chosen.
OBJECTIVES: To discuss concerns regarding the use of the existing definition of the MS (as defined in adults) in children and adolescents, analyzing the scientific evidence needed to detect a clustering of cardiovascular risk-factors. Finally, we propose a new methodological approach for estimating metabolic risk-factor clustering in children and adolescents.
RESULTS: Major concerns were the lack of information on the background derived from a child's family and personal history; the lack of consensus on insulin levels, lipid parameters, markers of inflammation or steato-hepatitis; the lack of an additive relevant effect of the MS definition to obesity per se. We propose the adoption of 10 evidence-based items from which to quantify metabolic risk-factor clustering, collected in a multilevel Metabolic Individual Risk-factor And CLustering Estimation (MIRACLE) approach, and thus avoiding the use of the current MS term in children.
CONCLUSION: Pediatricians should consider a novel and specific approach to assessing children/adolescents and should not simply derive or adapt definitions from adults. Evaluation of insulin and lipid levels should be included only when specific references for the relation of age, gender, pubertal status and ethnic origin to health risk become available. This new approach could be useful for improving the overall quality of patient evaluation and for optimizing the use of the limited resources available facing to the obesity epidemic
Anti-adipogenic activity of maackiain and ononin is mediated via inhibition of PPARγ in human adipocytes
No full textObesity is a global health burden for which we do not yet have effective treatments for prevention or therapy. Plants are an invaluable source of bioactive leads possessing anti-adipogenic potential. Ethnopharmacological use of Ononis spinosa L. roots (OSR) for treatment of obesity and metabolic disorders requires а scientific rationale. The current study examined the anti-adipogenic capacity of OSR and its secondary metabolites ononin (ONON) and maackiain (MACK) in human adipocytes as an in vitro model of obesity. Both ONON and MACK diminished lipid accumulation during adipocyte differentiation. Molecular docking analysis exposed the potential interactions between MACK or ONON and target regulatory adipogenic proteins. Furthermore, results from an RT-qPCR analysis disclosed significant upregulation of AMPK by MACK and ONON treatment. In addition, ONON increased SIRT1, PI3K and ACC mRNA expression, while MACK notably downregulated CEBPA, AKT, SREBP1, ACC and ADIPOQ. The protein level of PI3K, C/EBPα, PPARγ and adiponectin was reduced upon MACK treatment in a concentration-dependent manner. Similarly, ONON suppressed PI3K, PPARγ and adiponectin protein abundance. Finally, our study provides evidence that ONON exerts anti-adipogenic effect by upregulation of SIRT1 and inhibition of PI3K, PPARγ and adiponectin, while MACK induced strong inhibitory effect on adipogenesis via hampering PI3K, PPARγ/C/EBPα signaling and anti-lipogenic effect through downregulation of SREBP1 and ACC. Even though OSR does not hamper adipogenic differentiation, it could be exploited as a source of natural leads with anti-adipogenic potential. The multidirectional mechanism of action of MACK warrant further validation in the context of in vivo obesity models
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