Oxygen-glucose deprivation and reoxygenation on human cerebral organoids alters expression related to lipid metabolism

2020 ◽  
Author(s):  
Naoki Iwasa ◽  
Takeshi K. Matsui ◽  
Naritaka Morikawa ◽  
Yoshihiko M. Sakaguchi ◽  
Tomo Shiota ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Peroxisome Proliferator ◽  
Cerebral Tissue ◽  
Peroxisome Proliferator Activated Receptor ◽  
Induced Pluripotent ◽  
Effect Of Oxygen ◽  
Relationship Of ◽  
The Impact

AbstractIschemic stroke is one of the most common neurological disease. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown; due to a lack of ischemic human brain samples. In this study, we used cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). We identified 15 differentially expressed genes (DEGs); and found that all the DEGs were downregulated. Pathway analysis showed the relationship of vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor signaling pathway, and complement and coagulation cascades. These findings indicate the mechanisms underlying ischemic injury in human cerebral tissue.

scholarly journals Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and PKM2 as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation

2021 ◽  
Vol 15 ◽  
Author(s):  
Naoki Iwasa ◽  
Takeshi K. Matsui ◽  
Naohiko Iguchi ◽  
Kaoru Kinugawa ◽  
Naritaka Morikawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Signaling ◽  
The Impact

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed the relationships between vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and complement and coagulation cascades. Combinational verification with transcriptome and gene expression analysis of different cell types revealed fatty acids-related PPAR signaling pathway and pyruvate kinase isoform M2 (PKM2) as key markers of neuronal cells in response to OGD/R. These findings suggest that, although there remain some limitations to be improved, our ischemic stroke model using human cerebral organoids would be a potentially useful tool when combined with other conventional two-dimensional (2D) mono-culture systems.

scholarly journals The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6074
Author(s):  
Maciej Danielewski ◽  
Agnieszka Matuszewska ◽  
Adam Szeląg ◽  
Tomasz Sozański
Keyword(s):  
Transcription Factors ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Functions ◽  
The Impact

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

scholarly journals Zidovudine Impairs Adipogenic Differentiation through Inhibition of Clonal Expansion

2008 ◽  
Vol 52 (8) ◽  
pp. 2882-2889 ◽  
Author(s):  
Metodi V. Stankov ◽  
Reinhold E. Schmidt ◽  
Georg M. N. Behrens
Keyword(s):  
Adipogenic Differentiation ◽  
Clonal Expansion ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triglyceride Accumulation ◽  
Thymidine Incorporation Assay ◽  
Human Preadipocytes ◽  
Incorporation Assay ◽  
The Impact

ABSTRACT Lipoatrophy is a prevalent side effect of treatment with thymidine analogues. We wished to confine the time point of the antiadipogenic effect of zidovudine (AZT) during adipogenesis and to evaluate the antiproliferative effect of AZT on adipocyte homeostasis. We investigated the effects of AZT on adipogenesis in 3T3-F442A cells and studied their proliferation, differentiation, viability, and adiponectin expression. Cells were exposed to AZT (1 μM, 3 μM, 6 μM, and 180 μM), stavudine (d4T; 3 μM), or dideoxycytosine (ddC; 0.1 μM) for up to 15 days. Differentiation was assessed by real-time PCR and quantification of triglyceride accumulation. Proliferation and clonal expansion were determined by a [3H]thymidine incorporation assay. When they were induced to differentiate in the presence of AZT at the maximum concentration in plasma (C max) and lower concentrations, 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol and failed to express normal levels of the later adipogenic transcription factors, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ. AZT exerted an inhibitory effect on the completion of the mitotic clonal expansion, which resulted in incomplete 3T3-F442A differentiation and, finally, a reduction in the level of adiponectin expression. In addition, AZT impaired the constitutive proliferation in murine and primary human subcutaneous preadipocytes. In contrast, incubation with d4T and ddC at the C max did not affect either preadipocyte proliferation or clonal expansion and differentiation. We conclude that the antiproliferative and antiadipogenetic effects of AZT on murine and primary human preadipocytes reveal the impact of the drug on fat tissue regeneration. These effects of the drug are expected to contribute to disturbed adipose tissue homeostasis and to be influenced by differential drug concentration and penetration in individual patients.

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

scholarly journals Effects of 7°C environmental temperature acclimation during a 3-week training period

2020 ◽  
Vol 128 (4) ◽  
pp. 768-777
Author(s):  
Robert Shute ◽  
Katherine Marshall ◽  
Megan Opichka ◽  
Halee Schnitzler ◽  
Brent Ruby ◽  
...  
Keyword(s):  
Room Temperature ◽  
Environmental Temperature ◽  
Cellular Signaling ◽  
Temperature Acclimation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Training Adaptations ◽  
Before And After ◽  
The Impact ◽  
Environmental Temperatures

Cold environmental temperatures during exercise and recovery alter the acute response to cellular signaling and training adaptations. Approximately 3 wk is required for cold temperature acclimation to occur. To determine the impact of cold environmental temperature on training adaptations, fitness measurements, and aerobic performance, two groups of 12 untrained male subjects completed 1 h of cycling in 16 temperature acclimation sessions in either a 7°C or 20°C environmental temperature. Fitness assessments before and after acclimation occurred at standard room temperature. Muscle biopsies were taken from the vastus lateralis muscle before and after training to assess molecular markers related to mitochondrial development. Peroxisome proliferator-activated receptor-γ coactivator 1α ( PGC-1α) mRNA was higher in 7°C than in 20°C in response to acute exercise before training ( P = 0.012) but not after training ( P = 0.813). PGC-1α mRNA was lower after training ( P < 0.001). BNIP3 was lower after training in the 7°C than in the 20°C group ( P = 0.017) but not before training ( P = 0.549). No other differences occurred between temperature groups in VEGF, ERRα, NRF1, NRF2, TFAM, PINK1, Parkin, or BNIP3L mRNAs ( P > 0.05). PGC-1α protein and mtDNA were not different before training, after training, or between temperatures ( P > 0.05). Cycling power increased during the daily training ( P < 0.001) but was not different between temperatures ( P = 0.169). V̇o2peak increased with training ( P < 0.001) but was not different between temperature groups ( P = 0.460). These data indicate that a 3-wk period of acclimation/training in cold environmental temperatures alters PGC-1α gene expression acutely but this difference is not manifested in a greater increase in V̇o2peak and is dissipated as acclimation takes place. NEW & NOTEWORTHY This study examines the adaptive response of cellular signaling during exercise in cold environmental temperatures. We demonstrate that peroxisome proliferator-activated receptor-γ coactivator 1α mRNA is different between cold and room temperature environments before training but after training this difference no longer exists. This initial difference in transcriptional response between temperatures does not lead to differences in performance measures or increases in protein or mitochondria.

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