Pleiotrophin and metabolic disorders: insights into its role in metabolism

Ballesteros-Pla, Cristina; Sánchez-Alonso, María Gracia; Pizarro-Delgado, Javier; Zuccaro, Agata; Sevillano, Julio; Ramos-Álvarez, María Pilar

doi:10.3389/fendo.2023.1225150

Cited by 2 publications

(2 citation statements)

References 98 publications

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“…Of the genes identified in our internal bulk and single RNA-seq data only PTN, SLC7A8 and CDKN3 were also identified in mice datasets to be similarly expressed. PTN is a cytokine which when knocked out in high-fat diet fed mice, protects against insulin resistance, obesity and neuroinflammation Acharjee et al Journal of Translational Medicine (2024) 22:592 [52]. Similarly, deletion of SLC7A8 in mice offers significant protection against diet-induced obesity and enhances glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

Acharjee,

Wijesinghe,

Russ

et al. 2024

J Transl Med

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Background Fundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined ‘health weight’. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions. Methods The study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty. Results Principal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p < 0.05, identified differentially expressed genes (DEGs) in mouse and human datasets. DEGs were analysed further using area under curve (AUC) which identified 12 genes. Pathway enrichment analysis suggests these genes were involved in the biosynthesis and elongation of fatty acids and the transport, oxidation, and catabolic processing of lipids. qPCR validation found the majority of genes showed a tendency to be upregulated in joint tissues from obese participants. Three validated genes, IGFBP2 (p = 0.0363), DOK6 (0.0451) and CASP1 (0.0412) were found to be significantly different in obese joint tissues compared to lean-weight joint tissues. Conclusions The present study has employed machine learning models across several published obesity datasets to identify obesity-associated genes which are validated in joint tissues from OA. These results suggest obesity-associated genes are conserved across conditions and may be fundamental in accelerating disease in obese individuals. Whilst further validations and additional conditions remain to be tested in this model, identifying obesity-associated genes in this way may serve as a global aid for patient stratification giving rise to the potential of targeted therapeutic interventions in such patient subpopulations.

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Section: Discussionmentioning

confidence: 99%

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

Acharjee,

Wijesinghe,

Russ

et al. 2024

J Transl Med

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“…Inhibition of PTN expression in mouse embryonic pancreatic primordia explants prevented full maturation of endocrine precursors with impaired insulin and glucagon expression [ 727 ]. Further studies suggest a role for PTN in β-cell proliferation and regulation of glucose homeostasis [ 728 , 729 ]. BDNF has been shown to bind to the TrkB.T1 receptor on β-cells, resulting in increased GSIS [ 247 ].…”

Section: The Paracrine Function Of Mscsmentioning

confidence: 99%

A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome

Sionov,

Ahdut-HaCohen

2023

Biomedicines

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Type 1 Diabetes (T1D) is a chronic autoimmune disease characterized by a gradual destruction of insulin-producing β-cells in the endocrine pancreas due to innate and specific immune responses, leading to impaired glucose homeostasis. T1D patients usually require regular insulin injections after meals to maintain normal serum glucose levels. In severe cases, pancreas or Langerhans islet transplantation can assist in reaching a sufficient β-mass to normalize glucose homeostasis. The latter procedure is limited because of low donor availability, high islet loss, and immune rejection. There is still a need to develop new technologies to improve islet survival and implantation and to keep the islets functional. Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells with high plasticity that can support human pancreatic islet function both in vitro and in vivo and islet co-transplantation with MSCs is more effective than islet transplantation alone in attenuating diabetes progression. The beneficial effect of MSCs on islet function is due to a combined effect on angiogenesis, suppression of immune responses, and secretion of growth factors essential for islet survival and function. In this review, various aspects of MSCs related to islet function and diabetes are described.

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Pleiotrophin and metabolic disorders: insights into its role in metabolism

Cited by 2 publications

References 98 publications

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome

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