Polyamine metabolism and obesity: polyamine metabolic enzymes involved in obesity

Büyükuslu, Nihal; Öztürk, Rabia İclal

doi:10.23893/1307-2080.aps.05613

Cited by 5 publications

(8 citation statements)

References 30 publications

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“…L-ornithine, in turn, is used for the synthesis of carbamoyl phosphate in the urea cycle, or alternatively as a substrate for the synthesis of polyamine via ornithine decarboxylase-1 (ODC-1). Polyamines (spermine and spermidine) are required for mammalian cell proliferation [37,53] and are involved in the adipogenesis of preadipocytes (mouse fibroblast line 3T3-L1) [54][55][56]. We observed that the expression of ODC-1 increased along with the increase in SLC14A1 expression and with increased intracellular urea concentration after urea treatment.…”

Section: Discussionmentioning

confidence: 76%

Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells

Komrakova

Blaschke

Ponce

et al. 2020

Exp Clin Endocrinol Diabetes

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The human urea transporter SLC14A1 (HUT11/UT-B) has been suggested as a marker for the adipogenic differentiation of bone cells with a relevance for bone diseases. We investigated the function of SLC14A1 in different cells models from bone environment. SLC14A1 expression and cytokine production was investigated in bone cells obtained from patients with osteoporosis. Gene and protein expression of SLC14A1 was studied during adipogenic or osteogenic differentiation of human mesenchymal progenitor cells (hMSCs) and of the single-cell–derived hMSC line (SCP-1), as well as in osteoclasts and chondrocytes. Localization was determined by histochemical methods and functionality by urea transport experiments. Expression of SLC14A1 mRNA was lower in cells from patients with osteoporosis that produced high levels of cytokines. Accordingly, when adding a combination of cytokines to SCP-1 SLC14A1 mRNA expression decreased. SLC14A1 mRNA expression decreased after both osteogenic and more pronounced adipogenic stimulation of hMSCs and SCP-1 cells. The highest SLC14A1 expression was determined in undifferentiated cells, lowest in chondrocytes and osteoclasts. Downregulation of SLC14A1 by siRNA resulted in an increased expression of interleukin-6 and interleukin-1 beta as well as adipogenic markers. Urea influx through SLC14A1 increased expression of osteogenic markers, adipogenic markers were suppressed. SLC14A1 protein was localized in the cell membrane and the cytoplasm. Summarizing, the SLC14A1 urea transporter affects early differentiation of hMSCs by diminishing osteogenesis or by favoring adipogenesis, depending on its expression level. Therefore, SLC14A1 is not unequivocally an adipogenic marker in bone. Our findings suggest an involvement of SLC14A1 in bone metabolism and inflammatory processes and disease-dependent influences on its expression.

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Section: Discussionmentioning

confidence: 76%

Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells

Komrakova

Blaschke

Ponce

et al. 2020

Exp Clin Endocrinol Diabetes

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“…Considering the high requirement for polyamines in the first months of life, a stage of accelerated growth and development, and the potential participation of polyamines in adipogenesis ( 16 , 17 ), we studied if there was an association between the content of polyamines ingested through human milk and the infant anthropometric parameters. Most of the anthropometric indicators evaluated did not show significant correlations with the polyamine contents of human milk or polyamine intake, perhaps because all the infants in the study had an adequate nutritional status for their age, and anthropometric parameters were within normal limits (±2 SD).…”

Section: Discussionmentioning

confidence: 99%

“…SSAT catalyzes the transfer of acetyl groups from acetyl-CoA to spermidine or spermine, allowing polyamine interconversion (17,18). Thus, the dysregulation of polyamine homeostasis could have an important impact on energy metabolism and the accumulation of body fat (16,17). In fact, studies in mice report that overexpression of the SSAT enzyme caused a decrease in white adipose tissue (18,19), and the administration of spermidine or spermine reduced body weight and fat mass, in a dose-dependent manner (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

“…The enzyme spermidine/spermine N1-acetyltransferase (SSAT) is a key metabolic regulator in polyamine homeostasis and is strongly involved in adipogenesis. SSAT catalyzes the transfer of acetyl groups from acetyl-CoA to spermidine or spermine, allowing polyamine interconversion ( 17 , 18 ). Thus, the dysregulation of polyamine homeostasis could have an important impact on energy metabolism and the accumulation of body fat ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

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Influence of the Type of Breastfeeding and Human Milk Polyamines on Infant Anthropometric Parameters

et al. 2022

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Feeding choices in the early months of life are key determinants of growth during infancy. Polyamines participate in cell proliferation and differentiation, and it has also been suggested that polyamine metabolism plays a role in adipogenesis. As the main exogenous source of polyamines in the infant is human milk, the aim of this work was to study if the type of breastfeeding received and the polyamine intake from human milk has an influence on infant anthropometric parameters. A cohort of 78 full-term healthy newborns was followed up until 4 months of age; 55 were fully and 23 partially breastfed. Anthropometric measurements were taken at 2 and 4 months, when human milk samples were also collected for analysis of polyamine content by UHPLC-FL. Fully breastfed infants had a better anthropometric profile than those partially breastfed (p < 0.05). Furthermore, polyamine intake in partially breastfed infants was significantly lower compared to those fully breastfed. However, only two of the 15 anthropometric indicators evaluated (triceps skinfold and mean upper arm circumference) showed a significant inverse association with polyamine content in human milk and intake (p < 0.05). Infant growth and body composition differ according to the type of breastfeeding received. Based on the weak associations between polyamines and anthropometric indicators, it is not possible to conclude the influence of polyamines in infant growth and body composition.

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“…The prostate presents high levels of polyamines, and they increase in tumor tissues. In addition, it was shown that the inhibition of polyamine metabolism enzymes is associated with increased adipose tissue and weight gain in human and animal models ( 27 ). Alpha-difluoromethylornithine, an inhibitor of ODC, depleted the cellular polyamines and prevented triglyceride accumulation and differentiation in 3T3-L1 cells ( 28 ).…”

Section: Metabolism Dysfunction Of Periprostatic Adipose Tissue In Pr...mentioning

confidence: 99%

Periprostatic Adipose Tissue Microenvironment: Metabolic and Hormonal Pathways During Prostate Cancer Progression

Sacca

Calvo

2022

Front. Endocrinol.

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The periprostatic adipose tissue (PPAT) is a site of invasion of prostate cancer (PCa) and is part of the microenvironment. It was shown that PPAT secretes factors and fatty acids (FAs) that alter the microenvironment of the PCa. The PPAT secretome of patients with PCa-T3 stage (PPAT-T3) has a metabolic profile enriched in several pathways related to energy production, indicating a greater energy requirement by the tumor, when compared to that of patients in the PCa-T2 stage (PPAT-T2). PPAT-T3 also shows enrichment in pathways related to hormone response, polyamine synthesis, and control of protein synthesis, through amino acid, RNA, and nucleotide metabolism. PPAT-T2 and PPAT-BPH secretomes have less complex metabolic profile, both related with energy balance, while PPAT-BPH has hormone response through insulin pathway. Undoubtedly, a deeper characterization of the human PPAT will lead to a better understanding of the disease and possibly allow new stratification factors and the design of a specific therapy that targets crucial components of the tumor microenvironment as another way to treat or control the disease.

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Polyamine metabolism and obesity: polyamine metabolic enzymes involved in obesity

Cited by 5 publications

References 30 publications

Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells

Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells

Influence of the Type of Breastfeeding and Human Milk Polyamines on Infant Anthropometric Parameters

Periprostatic Adipose Tissue Microenvironment: Metabolic and Hormonal Pathways During Prostate Cancer Progression

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