bims-stacyt 2021-06-06 papers

Metabolites. 2021 May 13. pii: 311. [Epub ahead of print]11(5):

High Glucose Shifts the Oxylipin Profiles in the Astrocytes towards Pro-Inflammatory States.

Dmitry V Chistyakov, Sergei V Goriainov, Alina A Astakhova, Marina G Sergeeva.

Hyperglycemia is associated with several complications in the brain, which are also characterized by inflammatory conditions. Astrocytes are responsible for glucose metabolism in the brain and are also important participants of inflammatory responses. Oxylipins are lipid mediators, derived from the metabolism of polyunsaturated fatty acids (PUFAs) and are generally considered to be a link between metabolic and inflammatory processes. High glucose exposure causes astrocyte dysregulation, but its effects on the metabolism of oxylipins are relatively unknown and therefore, constituted the focus of our work. We used normal glucose (NG, 5.5 mM) vs. high glucose (HG, 25 mM) feeding media in primary rat astrocytes-enriched cultures and measured the extracellular release of oxylipins (UPLC-MS/MS) in response to lipopolysaccharide (LPS). The sensitivity of HG and NG growing astrocytes in oxylipin synthesis for various serum concentrations was also tested. Our data reveal shifts towards pro-inflammatory states in HG non-stimulated cells: an increase in the amounts of free PUFAs, including arachidonic (AA), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, and cyclooxygenase (COX) mediated metabolites. Astrocytes cultivated in HG showed a tolerance to the LPS, and an imbalance between inflammatory cytokine (IL-6) and oxylipins release. These results suggest a regulation of COX-mediated oxylipin synthesis in astrocytes as a potential new target in treating brain impairment associated with hyperglycemia.

Keywords: astrocytes; eicosanoids; high glucose; inflammation; interleukin 6 (IL-6); oxylipins; tolerance; toll-like receptors (TLRs)

DOI: https://doi.org/10.3390/metabo11050311

Cell Metab. 2021 Jun 01. pii: S1550-4131(21)00227-8. [Epub ahead of print]33(6): 1071-1072

Can tumor cells take it all away?

Anna Kohl, Kung-Chi Kao, Ping-Chih Ho.

Tumor cells utilize glucose to engage in aerobic glycolysis, fulfilling their metabolic demands for extensive proliferation. A recent study in Nature discovers that tumor-infiltrating myeloid cells exhibit a superior glucose uptake capacity over tumor cells, which present enhanced glutamine metabolism, suggesting that nutrient partitioning in the TME might be more complex than previously thought.

DOI: https://doi.org/10.1016/j.cmet.2021.05.010

Clin Sci (Lond). 2021 Jun 11. 135(11): 1389-1408

Cholesterol metabolism: a new molecular switch to control inflammation.

Diana Cardoso, Esperanza Perucha.

The immune system protects the body against harm by inducing inflammation. During the immune response, cells of the immune system get activated, divided and differentiated in order to eliminate the danger signal. This process relies on the metabolic reprogramming of both catabolic and anabolic pathways not only to produce energy in the form of ATP but also to generate metabolites that exert key functions in controlling the response. Equally important to mounting an appropriate effector response is the process of immune resolution, as uncontrolled inflammation is implicated in the pathogenesis of many human diseases, including allergy, chronic inflammation and cancer. In this review, we aim to introduce the reader to the field of cholesterol immunometabolism and discuss how both metabolites arising from the pathway and cholesterol homeostasis are able to impact innate and adaptive immune cells, staging cholesterol homeostasis at the centre of an adequate immune response. We also review evidence that demonstrates the clear impact that cholesterol metabolism has in both the induction and the resolution of the inflammatory response. Finally, we propose that emerging data in this field not only increase our understanding of immunometabolism but also provide new tools for monitoring and intervening in human diseases, where controlling and/or modifying inflammation is desirable.

Keywords: Inflammation; cholesterol; immune system; immunometabolism; immunomodulation; metabolism

DOI: https://doi.org/10.1042/CS20201394

Mol Cell Biochem. 2021 May 29.

The inflammatory signalling mediator TAK1 mediates lymphocyte recruitment to lipopolysaccharide-activated murine mesenchymal stem cells through interleukin-6.

Beatrice Oelze, Kirsten Elger, Patrik Schadzek, Laura Burmeister, Anika Hamm, Sandra Laggies, Virginia Seiffart, Gerhard Gross, Andrea Hoffmann.

As a response to pro-inflammatory signals mesenchymal stem cells (MSCs) secrete agents and factors leading to lymphocyte recruitment, counteracting inflammation, and stimulating immunosuppression. On a molecular level, the signalling mediator TGF-β-activated kinase 1 (TAK1) is activated by many pro-inflammatory signals, plays a critical role in inflammation and regulates innate and adaptive immune responses as well. While the role of TAK1 as a signalling factor promoting inflammation is well documented, we also considered a role for TAK1 in anti-inflammatory actions exerted by activated MSCs. We, therefore, investigated the capacity of lipopolysaccharide (LPS)-treated murine MSCs with lentivirally modulated TAK1 expression levels to recruit lymphocytes. TAK1 downregulated by lentiviral vectors expressing TAK1 shRNA in murine MSCs interfered with the capacity of murine MSCs to chemoattract lymphocytes, indeed. Analysing a pool of 84 secreted factors we found that among 26 secreted cytokines/factors TAK1 regulated expression of one cytokine in LPS-activated murine MSCs in particular: interleukin-6 (IL-6). IL-6 in LPS-treated MSCs was responsible for lymphocyte recruitment as substantiated by neutralizing antibodies. Our studies, therefore, suggest that in LPS-treated murine MSCs the inflammatory signalling mediator TAK1 may exert anti-inflammatory properties via IL-6.

Keywords: Differentiation; Infection; Inflammation; Promiscuous function of TAK1

DOI: https://doi.org/10.1007/s11010-021-04180-8

PeerJ. 2021 ;9 e11305

High fructose exposure modifies the amount of adipocyte-secreted microRNAs into extracellular vesicles in supernatants and plasma.

Adrián Hernández-Díazcouder, Javier González-Ramírez, Abraham Giacoman-Martínez, Guillermo Cardoso-Saldaña, Eduardo Martínez-Martínez, Horacio Osorio-Alonso, Ricardo Márquez-Velasco, José L Sánchez-Gloria, Yaneli Juárez-Vicuña, Guillermo Gonzaga, Laura Gabriela Sánchez-Lozada, Julio César Almanza-Pérez, Fausto Sánchez-Muñoz.

Background: High fructose exposure induces metabolic and endocrine responses in adipose tissue. Recent evidence suggests that microRNAs in extracellular vesicles are endocrine signals secreted by adipocytes. Fructose exposure on the secretion of microRNA by tissues and cells is poorly studied. Thus, the aim of this study was to evaluate the effect of fructose exposure on the secretion of selected microRNAs in extracellular vesicles from 3T3-L1 cells and plasma from Wistar rats.Methods: 3T3-L1 cells were exposed to 550 µM of fructose or standard media for four days, microRNAs levels were determined in extracellular vesicles of supernatants and cells by RT-qPCR. Wistar rats were exposed to either 20% fructose drink or tap water for eight weeks, microRNAs levels were determined in extracellular vesicles of plasma and adipose tissue by RT-qPCR.
Results: This study showed that fructose exposure increased the total number of extracellular vesicles released by 3T3-L1 cells (p = 0.0001). The levels of miR-143-5p were increased in extracellular vesicles of 3T3-L1 cells exposed to fructose (p = 0.0286), whereas miR-223-3p levels were reduced (p = 0.0286). Moreover, in plasma-derived extracellular vesicles, miR-143-5p was higher in fructose-fed rats (p = 0.001), whereas miR-223-3p (p = 0.022), miR-342-3p (p = 0.0011), miR-140-5p (p = 0.0129) and miR-146b-5p (p = 0.0245) were lower.
Conclusion: Fructose exposure modifies the levels of microRNAs in extracellular vesicles in vitro and in vivo. In particular, fructose exposure increases miR-143-5p, while decreases miR-223-3p and miR-342-3p.

Keywords: Adipocytes; Adipose tissue; Extracellular Vesicles; Fructose; microRNA

DOI: https://doi.org/10.7717/peerj.11305