bims-polyam 2021-08-08 papers

Issue of 2021–08–08
five papers selected by
Sebastian J. Hofer, University of Graz

Cell. 2021 Aug 05. pii: S0092-8674(21)00838-2. [Epub ahead of print]184(16): 4109-4112

Polyamine: A metabolic compass for T helper cell fate direction.

Interplay between metabolic and epigenetic remodeling may be key to cell fate control. In this issue of Cell, Puleston et al. and Wagner et al. use metabolomic, computational, and genetic approaches to uncover that polyamine metabolism directs T helper cell lineage choices, epigenetic state, and pathogenic potential in inflammation.

DOI: https://doi.org/10.1016/j.cell.2021.07.012

Mol Nutr Food Res. 2021 Aug 07. e2100315

Oral Spermidine Targets Brown Fat and Skeletal Muscle to Mitigate Diet-Induced Obesity and Metabolic Disorders.

Di Wang, Jilong Yin, Zixin Zhou, Yan Tao, Yufeng Jia, Haipeng Jie, Jingyuan Zhao, Ruiyu Li, Yuan Li, Chun Guo, Faliang Zhu, Haiting Mao, Lining Zhang, Qun Wang.

SCOPE: Obesity causes many life-threatening diseases. It is important to develop effective approaches for obesity treatment. Oral supplementation with spermidine retards age-related processes, but its influences on obesity and various metabolic tissues remain largely unknow. This study aims to investigate the effects of oral spermidine on brown adipose tissue (BAT) and skeletal muscle as well as its roles in counteracting obesity and metabolic disorders.
METHODS AND RESULTS: Spermidine was orally administrated into high-fat diet (HFD)-fed mice. The weight gain, insulin resistance and hepatic steatosis were attenuated by oral spermidine in HFD-fed mice, accompanied by an alleviation of white adipose tissue inflammation. Oral spermidine promoted BAT activation and metabolic adaptation of skeletal muscle in HFD-fed mice, evidenced by UCP-1 induction and CREB activation in both tissues. Notably, oral spermidine upregulated tyrosine hydroxylase in hypothalamus of HFD-fed mice; spermidine treatment increased tyrosine hydroxylase expression and norepinephrine production in neurocytes, which led to CREB activation and UCP-1 induction in brown adipocytes and myotubes. Spermidine also directly promoted UCP-1 and PGC-1α expression in brown adipocytes and myotubes.
CONCLUSION: Spermidine serves as an oral supplement to attenuate obesity and metabolic disorders through hypothalamus-dependent or -independent BAT activation and skeletal muscle adaptation. This article is protected by copyright. All rights reserved.

Keywords: brown adipose tissue; hypothalamus; obesity; oral spermidine; skeletal muscle

DOI: https://doi.org/10.1002/mnfr.202100315

Insects. 2021 Jul 08. pii: 624. [Epub ahead of print]12(7):

Function of Polyamines in Regulating Cell Cycle Progression of Cultured Silkworm Cells.

Li Chang, Zhiqing Li, Hao Guo, Wenchang Zhang, Weiqun Lan, Jue Wang, Guanwang Shen, Qingyou Xia, Ping Zhao.

BACKGROUND: Putrescine, spermidine, and spermine are polyamines that are ubiquitously distributed in prokaryotic and eukaryotic cells, which play important roles in cell proliferation and differentiation.
METHODS: We investigated the expression profiles of polyamine pathway genes by qRT-PCR in different tissues of the lepidopteran silkworm. The polyamine levels in cultured silkworm cells were measured by HPLC. Spermidine and polyamine biosynthetic inhibitors were used for treating the cultured silkworm cells in order to clarify their effects on cell cycle progression.
RESULTS: We identified the anabolic and catabolic enzymes that are involved in the polyamine biosynthetic pathway in silkworm. Transcriptional expression showed at least seven genes that were expressed in different silkworm tissues. Treatments of the cultured silkworm cells with spermidine or inhibitor mixtures of DFMO and MGBG induced or inhibited the expression of cell cycle-related genes, respectively, and thus led to changed progression of the cell cycle.
CONCLUSIONS: The present study is the first to identify the polyamine pathway genes and to demonstrate the roles of polyamines on cell cycle progression via regulation of the expression of cell cycle genes in silkworm.

Keywords: Bombyx mori; cell cycle progression; polyamines

DOI: https://doi.org/10.3390/insects12070624

Microb Pathog. 2021 Jul 29. pii: S0882-4010(21)00388-0. [Epub ahead of print] 105114

Host metabolic reprogramming in response to SARS-CoV-2 infection: A systems biology approach.

S T R Moolamalla, Rami Balasubramanian, Ruchi Chauhan, U Deva Priyakumar, P K Vinod.

Understanding the pathogenesis of SARS-CoV-2 is essential for developing effective treatment strategies. Viruses hijack the host metabolism to redirect the resources for their replication and survival. The influence of SARS-CoV-2 on host metabolism is yet to be fully understood. In this study, we analyzed the transcriptomic data obtained from different human respiratory cell lines and patient samples (nasopharyngeal swab, peripheral blood mononuclear cells, lung biopsy, bronchoalveolar lavage fluid) to understand metabolic alterations in response to SARS-CoV-2 infection. We explored the expression pattern of metabolic genes in the comprehensive genome-scale network model of human metabolism, Recon3D, to extract key metabolic genes, pathways, and reporter metabolites under each SARS-CoV-2-infected condition. A SARS-CoV-2 core metabolic interactome was constructed for network-based drug repurposing. Our analysis revealed the host-dependent dysregulation of glycolysis, mitochondrial metabolism, amino acid metabolism, nucleotide metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. We observed different pro- and antiviral metabolic changes and generated hypotheses on how the host metabolism can be targeted for reducing viral titers and immunomodulation. These findings warrant further exploration with more samples and in vitro studies to test predictions.

Keywords: COVID-19; Host-pathogen interaction; Polyamine metabolism; Redox homeostasis; Transcriptomics; Warburg effect

DOI: https://doi.org/10.1016/j.micpath.2021.105114

Oxid Med Cell Longev. 2021 ;2021 5550196

Methionine Protects Mammary Cells against Oxidative Stress through Producing S-Adenosylmethionine to Maintain mTORC1 Signaling Activity.

Heju Zhong, Peiqiang Yuan, Yunxia Li, Dolores Batonon-Alavo, Caroline Deschamps, Bin Feng, Xiaoling Zhang, Lianqiang Che, Yan Lin, Shengyu Xu, Jian Li, Yong Zhuo, Gang Tian, Jiayong Tang, Xuemei Jiang, Lingjie Huang, Caimei Wu, De Wu, Zhengfeng Fang.

The mechanistic target of rapamycin complex 1 (mTORC1) signaling plays pivotal roles in cell growth and diseases. However, it remains mechanistically unclear about how to maintain mTORC1 activity during mammary glands development. Here we showed that mammary glands suffered from aggravated oxidative stress as pregnancy advanced and was accompanied by an increase in H2O2 levels, while the consumption for methionine and S-adenosylmethionine (SAM) rather than S-adenosylhomocysteine (SAH) were promoted in vivo. Likewise, H2O2 promoted SAM synthesis and reduced SAM utilization for methylation depending on H2O2 levels and treatment time in vitro. H2O2 inhibited phosphorylation of S6 kinase Thr 389 (p-S6K1 (T389)), 4E-BP1 Thr 37/46 and ULK1 Ser 757, the downstream of mTORC1, in mammary epithelial cells. However, methionine and SAM were shown to activate mTORC1 under H2O2-exposed condition. Moreover, this effect was not disabled by SGI-1027 which inhibits SAM transmethylation. In conclusion, methionine appeared to protect mammary cells against oxidative stress through producing SAM to maintain mTORC1 signaling activity.

DOI: https://doi.org/10.1155/2021/5550196