bims-stacyt 2021-12-12 papers

Int J Mol Sci. 2021 Nov 23. pii: 12668. [Epub ahead of print]22(23):

Regulation of the Fructose Transporter Gene Slc2a5 Expression by Glucose in Cultured Microglial Cells.

Tooru M Mizuno, Pei San Lew, Gursagar Jhanji.

Microglia play a role in the regulation of metabolism and pathogenesis of obesity. Microglial activity is altered in response to changes in diet and the body's metabolic state. Solute carrier family 2 member 5 (Slc2a5) that encodes glucose transporter 5 (GLUT5) is a fructose transporter primarily expressed in microglia within the central nervous system. However, little is known about the nutritional regulation of Slc2a5 expression in microglia and its role in the regulation of metabolism. The present study aimed to address the hypothesis that nutrients affect microglial activity by altering the expression of glucose transporter genes. Murine microglial cell line SIM-A9 cells and primary microglia from mouse brain were exposed to different concentrations of glucose and levels of microglial activation markers and glucose transporter genes were measured. High concentration of glucose increased levels of the immediate-early gene product c-Fos, a marker of cell activation, Slc2a5 mRNA, and pro-inflammatory cytokine genes in microglial cells in a time-dependent manner, while fructose failed to cause these changes. Glucose-induced changes in pro-inflammatory gene expression were partially attenuated in SIM-A9 cells treated with the GLUT5 inhibitor. These findings suggest that an increase in local glucose availability leads to the activation of microglia by controlling their carbohydrate sensing mechanism through both GLUT5-dependent and -independent mechanisms.

Keywords: fructose; glucose; microglia; nutrient; obesity

DOI: https://doi.org/10.3390/ijms222312668

Adv Exp Med Biol. 2021 ;1350 101-121

Metabolic Interactions Between Tumor and Stromal Cells in the Tumor Microenvironment.

Deepshikha Mishra, Debabrata Banerjee.

In this chapter, we provide information about metabolic reprogramming in cancer cells, molecular interactions between tumor and stromal cells in the tumor microenvironment, focusing primarily on CAFs and tumor cell interaction. We have covered the role of cytokines, chemokines, and lactate in driving tumor-stroma interactions in the microenvironment. Here, we have discussed the pro-tumorigenic molecular interactions in between tumor cells and CAFs mediated via altered signaling pathways, cytokines, chemokines, and lactate in the tumor vicinity. A better understanding of the complex cancer cell-CAF interactions will help in designing successful therapeutic strategies targeting the stromal-rich tumors in the clinic.

Keywords: CAFs; Cytokines; Lactate; Metabolic cooperation; Pyruvate; Tumor microenvironment

DOI: https://doi.org/10.1007/978-3-030-83282-7_5

Int J Mol Sci. 2021 Nov 29. pii: 12898. [Epub ahead of print]22(23):

Effects of Intermittent Hypoxia on Cytokine Expression Involved in Insulin Resistance.

Tomoko Uchiyama, Hiroyo Ota, Chiho Ohbayashi, Shin Takasawa.

Sleep apnea syndrome (SAS) is a prevalent disorder characterized by recurrent apnea or hypoxia episodes leading to intermittent hypoxia (IH) and arousals during sleep. Currently, the relationship between SAS and metabolic diseases is being actively analyzed, and SAS is considered to be an independent risk factor for the development and progression of insulin resistance/type 2 diabetes (T2DM). Accumulating evidence suggests that the short cycles of decreased oxygen saturation and rapid reoxygenation, a typical feature of SAS, contribute to the development of glucose intolerance and insulin resistance. In addition to IH, several pathological conditions may also contribute to insulin resistance, including sympathetic nervous system hyperactivity, oxidative stress, vascular endothelial dysfunction, and the activation of inflammatory cytokines. However, the detailed mechanism by which IH induces insulin resistance in SAS patients has not been fully revealed. We have previously reported that IH stress may exacerbate insulin resistance/T2DM, especially in hepatocytes, adipocytes, and skeletal muscle cells, by causing abnormal cytokine expression/secretion from each cell. Adipose tissues, skeletal muscle, and the liver are the main endocrine organs producing hepatokines, adipokines, and myokines, respectively. In this review, we focus on the effect of IH on hepatokine, adipokine, and myokine expression.

Keywords: adipokines; hepatokines; insulin resistance; intermittent hypoxia; myokines; sleep apnea syndrome

DOI: https://doi.org/10.3390/ijms222312898

iScience. 2021 Dec 17. 24(12): 103448

Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity.

Masato Miyake, Jun Zhang, Akihiro Yasue, Satoshi Hisanaga, Kazue Tsugawa, Hiroshi Sakaue, Miho Oyadomari, Hiroshi Kiyonari, Seiichi Oyadomari.

The eIF2α phosphorylation-dependent integrated stress response (ISR) is a signaling pathway that maintains homeostasis in mammalian cells exposed to various stresses. Here, ISR activation in adipocytes improves obesity and diabetes by regulating appetite in a non-cell-autonomous manner. Adipocyte-specific ISR activation using transgenic mice decreases body weight and improves glucose tolerance and obesity induced by a high-fat diet (HFD) via preferential inhibition of HFD intake. The transcriptome analysis of ISR-activated adipose tissue reveals that growth differentiation factor 15 (GDF15) expression is induced by the ISR through the direct regulation of the transcription factors ATF4 and DDIT3. Deficiency in the GDF15 receptor GFRAL abolishes the adipocyte ISR-dependent preferential inhibition of HFD intake and the anti-obesity effects. Pharmacologically, 10(E), 12(Z)-octadecadienoic acid induces ISR-dependent GDF15 expression in adipocytes and decreases the intake of the HFD. Based on our findings the specific activation of the ISR in adipocytes controls the non-cell-autonomous regulation of appetite.

Keywords: Biological sciences; Cell biology; Human metabolism

DOI: https://doi.org/10.1016/j.isci.2021.103448