SMOX and SMS Responsible for Polyamine Metabolism Enhanced Adipogenesis

Abstract Adipose tissue regulating carbohydrate and lipid metabolism had been extensively focused. However, the regulation of amino acid metabolism during adipocyte differentiation remained detailed. Here we applied RNA-Seq technique to establish the transcriptional landscapes of amino acid metabolism during adipogenesis. We totally screened 17 differentially expressed genes (DEGs) for amino acid metabolism at 7, 14, 21, and 28 days during adipogenesis from human mesenchymal stem cells (hMSCs), especially with 13 up-regulated genes most prevalent in our adipogenic anecdote. Small molecule metabolic process was the most enriched biological process following by oxidation-reduction process. Interestingly, the enforced expression of SMOX (spermine oxidase) responsible for polyamine metabolism in arginine and proline metabolism pathway facilitated adipogenesis more than SMS (spermine synthase) using RNA interference (RNAi). The established potential regulatory network further suggested that adipocyte differentiation tightly related with the basal metabolism of amino acid metabolism with the partially confirmed SMS-SMOX-PPARG signaling pathway. It would highlight the effect of adipogenesis on amino acid metabolism in adipocyte biology and provide the potential treatment strategy for the study of fat metabolic diseases.

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Glucagon Receptor Signaling and Glucagon Resistance

International Journal of Molecular Sciences ◽

10.3390/ijms20133314 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3314 ◽

Cited By ~ 18

Author(s):

Janah ◽

Kjeldsen ◽

Galsgaard ◽

Winther-Sørensen ◽

Stojanovska ◽

...

Keyword(s):

Lipid Metabolism ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Metabolic Diseases ◽

Physiological Role ◽

Glucagon Receptor ◽

Metabolomic Profiling ◽

Hepatic Fat

Hundred years after the discovery of glucagon, its biology remains enigmatic. Accurate measurement of glucagon has been essential for uncovering its pathological hypersecretion that underlies various metabolic diseases including not only diabetes and liver diseases but also cancers (glucagonomas). The suggested key role of glucagon in the development of diabetes has been termed the bihormonal hypothesis. However, studying tissue-specific knockout of the glucagon receptor has revealed that the physiological role of glucagon may extend beyond blood-glucose regulation. Decades ago, animal and human studies reported an important role of glucagon in amino acid metabolism through ureagenesis. Using modern technologies such as metabolomic profiling, knowledge about the effects of glucagon on amino acid metabolism has been expanded and the mechanisms involved further delineated. Glucagon receptor antagonists have indirectly put focus on glucagon’s potential role in lipid metabolism, as individuals treated with these antagonists showed dyslipidemia and increased hepatic fat. One emerging field in glucagon biology now seems to include the concept of hepatic glucagon resistance. Here, we discuss the roles of glucagon in glucose homeostasis, amino acid metabolism, and lipid metabolism and present speculations on the molecular pathways causing and associating with postulated hepatic glucagon resistance.

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Emerging perspectives on branched-chain amino acid metabolism during adipocyte differentiation

Current Opinion in Clinical Nutrition & Metabolic Care ◽

10.1097/mco.0000000000000429 ◽

2018 ◽

Vol 21 (1) ◽

pp. 49-57 ◽

Cited By ~ 6

Author(s):

Daniela Salinas-Rubio ◽

Armando R. Tovar ◽

Lilia G. Noriega

Keyword(s):

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Adipocyte Differentiation ◽

Branched Chain Amino Acid ◽

Branched Chain

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Patterns of Amino Acid Metabolism by Proliferating Human Mesenchymal Stem Cells

Tissue Engineering Part A ◽

10.1089/ten.tea.2011.0223 ◽

2012 ◽

Vol 18 (5-6) ◽

pp. 654-664 ◽

Cited By ~ 23

Author(s):

Gustavo A. Higuera ◽

Deborah Schop ◽

Tim W.G.M. Spitters ◽

Riemke van Dijkhuizen-Radersma ◽

Madelon Bracke ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Human Mesenchymal Stem Cells

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Hepatic SRC-1 Activity Orchestrates Transcriptional Circuitries of Amino Acid Pathways with Potential Relevance for Human Metabolic Pathogenesis

Molecular Endocrinology ◽

10.1210/me.2014-1083 ◽

2014 ◽

Vol 28 (10) ◽

pp. 1707-1718 ◽

Cited By ~ 6

Author(s):

Mounia Tannour-Louet ◽

Brian York ◽

Ke Tang ◽

Erin Stashi ◽

Hichem Bouguerra ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Metabolic Diseases ◽

Clinical Symptoms ◽

Missense Variant ◽

Tyrosine Aminotransferase ◽

Quantitative Metabolomics ◽

Steroid Receptor Coactivator

Disturbances in amino acid metabolism are increasingly recognized as being associated with, and serving as prognostic markers for chronic human diseases, such as cancer or type 2 diabetes. In the current study, a quantitative metabolomics profiling strategy revealed global impairment in amino acid metabolism in mice deleted for the transcriptional coactivator steroid receptor coactivator (SRC)-1. Aberrations were hepatic in origin, because selective reexpression of SRC-1 in the liver of SRC-1 null mice largely restored amino acids concentrations to normal levels. Cistromic analysis of SRC-1 binding sites in hepatic tissues confirmed a prominent influence of this coregulator on transcriptional programs regulating amino acid metabolism. More specifically, SRC-1 markedly impacted tyrosine levels and was found to regulate the transcriptional activity of the tyrosine aminotransferase (TAT) gene, which encodes the rate-limiting enzyme of tyrosine catabolism. Consequently, SRC-1 null mice displayed low TAT expression and presented with hypertyrosinemia and corneal alterations, 2 clinical features observed in the human syndrome of TAT deficiency. A heterozygous missense variant of SRC-1 (p.P1272S) that is known to alter its coactivation potential, was found in patients harboring idiopathic tyrosinemia-like disorders and may therefore represent one risk factor for their clinical symptoms. Hence, we reinforce the concept that SRC-1 is a central factor in the fine orchestration of multiple pathways of intermediary metabolism, suggesting it as a potential therapeutic target that may be exploitable in human metabolic diseases and cancer.

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