F13A1 transglutaminase expression in human adipose tissue increases in acquired excess weight and associates with inflammatory status of adipocytes

Kaartinen, Mari T.; Arora, Mansi; Heinonen, Sini; Hang, Anny; Barry, Amadou; Lundbom, Jesper; Hakkarainen, Antti; Lundholm, Nina; Rissanen, Aila; Kaprio, Jaakko; Pietiläinen, Kirsi H.

doi:10.1038/s41366-020-00722-0

Cited by 21 publications

(9 citation statements)

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“…F13A1, also known as coagulation factor XIII A chain, is a cellular process involved in the degradation and recycling of damaged cellular components. Studies have shown that F13A1 was signi cantly altered, with higher expression in adipose tissue, linking to increased weight, pro-in ammatory, cell stress, and tissue remodeling pathways [38,39]. FGR is a gene that encodes the FGR protein, which is a member of the Src family of non-receptor protein tyrosine kinases.…”

Section: Discussionmentioning

confidence: 99%

Interaction between N6-methyladenosine and autophagy in the immune infiltration and subtype classification of thyroid eye disease

Zhao

Gong

Chen

2023

Preprint

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Background:Thyroid eye disease (TED) is a chronic inflammatory autoimmune disease with a complex etiology. N6-methyladenosine (m6A) modification and autophagy were confirmed separately to be involved in the TED process. Increased evidence has shown that m6A is critical in regulating autophagy in various diseases. However, there is limited knowledge about the interactive effects of m6A modification and autophagy in TED. Our research aimed to investigate the effects of m6A modification and autophagy interactivity in TED. Results: We first identified dysregulation of five m6A regulators and 44 ARGs in TED patients compared to healthy controls. After correlation analysis, overlapping with the validated target genes from the RM2target database, and verification in our samples, FTO and BNIP3 were considered biomarkers for TED. Subsequently, based on dysregulated m6A regulators and ARGs separately, we classified 27 TED patients into two clusters, and the immune infiltration characteristics of clusters were further evaluated. Cluster-related differentially expressed genes were identified, and the enriched biological functions and pathways were elucidated. In addition, using two machine learning algorithms, we created a prediction model for TED patients with different molecular clusters. The nomogram, calibration curve, and decision curve analysis were performed to assess the performance of the predictive model. Conclusions: This study revealed that an interactive effect between FTO and BNIP3, suppressed FTO might downregulate the expression of BNIP3 in an m6A-dependent manner, inhibiting the autophagy and subsequently promoting the TED process. In addition, we constructed a nomogram model in predicting the TED. These results provide new insights into understanding the mechanism of TED.

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Section: Discussionmentioning

confidence: 99%

Interaction between N6-methyladenosine and autophagy in the immune infiltration and subtype classification of thyroid eye disease

Zhao

Gong

Chen

2023

Preprint

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“…CYP1B1 is involved in metabolism of steroids and fatty acids; its knockdown in mice reduces development of obesity in response to a high-fat diet ( Liu et al, 2015 ). F13A1 encodes transglutaminase FXIII-A, which is associated with adipose tissue hypertrophy and expression of components of cell stress and tissue remodeling pathways in humans ( Kaartinen et al, 2021 ). F13A1 expression is negatively associated with adiponectin in humans, consistent with our findings that F13A1 was more highly expressed in outer blubber, while ADIPOQ was more highly expressed in inner blubber of seals.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive molecular and morphological resolution of blubber stratification in a deep-diving, fasting-adapted seal

et al. 2022

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Blubber is a modified subcutaneous adipose tissue in marine mammals that provides energy storage, thermoregulation, hydrodynamic locomotion, and buoyancy. Blubber displays vertical stratification by lipid content, fatty acid composition, and vascularization, leading to the assumption that deeper blubber layers are metabolically active, while superficial layers are mainly structural and thermoregulatory. However, few studies have examined functional stratification of marine mammal blubber directly, especially in pinnipeds. We characterized morphological and transcriptional differences across blubber layers in the northern elephant seal, a deep-diving and fasting-adapted phocid. We collected blubber from seals early in their fasting period and divided blubber cores into three similarly sized portions. We hypothesized that the innermost blubber portion would have higher 1) heterogeneity in adipocyte size, 2) microvascular density, and 3) expression of genes associated with metabolism and hormone signaling than outer blubber. We found that adipocyte area and variance increased from outermost (skin-adjacent) to innermost (muscle-adjacent) blubber layers, suggesting that inner blubber has a higher capacity for lipid storage and turnover than outer blubber. Inner blubber had a higher proportion of CD144+ endothelial cells, suggesting higher microvascular density. In contrast, outer blubber had a higher proportion of CD4+ immune cells than inner blubber, suggesting higher capacity for response to tissue injury. Transcriptome analysis identified 61 genes that were differentially expressed between inner and outer blubber layers, many of which have not been studied previously in marine mammals. Based on known functions of these genes in other mammals, we suggest that inner blubber has potentially higher 1) adipogenic capacity, 2) cellular diversity, and 3) metabolic and neuroendocrine signaling activity, while outer blubber may have higher 1) extracellular matrix synthesis activity and 2) responsiveness to pathogens and cell stressors. We further characterized expression of nine genes of interest identified by transcriptomics and two adipokines with higher precision across blubber layers using targeted assays. Our study provides functional insights into stratification of blubber in marine mammals and a molecular key, including CD144, CD4, HMGCS2, GABRG2, HCAR2, and COL1A2, for distinguishing blubber layers for physiological and functional studies in seals.

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“…MAC2 were enriched for CD163, a marker for perivascular macrophage, TGFBI, MRC1/CD206, and F13A1. Both, CD206+ and F13A1+ macrophages, have been associated with AT dysfunction, pro-inflammatory responses, and AT remodeling in human obesity (Kaartinen et al, 2021;Muir et al, 2022). SAT-specific MAC3 was majorly characterized by Frontiers in Cell and Developmental Biology frontiersin.org ABL1, which's expression regulates macrophage podosome formation, SPTBN1, ZBTB16, and ADAMTSL3.…”

Section: Macrophages Are the Predominant Immune Cell Type In Vat And ...mentioning

confidence: 99%

Single-nuclei analysis reveals depot-specific transcriptional heterogeneity and depot-specific cell types in adipose tissue of dairy cows

Michelotti

Kisby

Flores

et al. 2022

Front. Cell Dev. Biol.

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Adipose tissue (AT) is an endocrine organ with a central role on whole-body energy metabolism and development of metabolic diseases. Single-cell and single-nuclei RNA sequencing (scRNA-seq and snRNA-seq, respectively) analyses in mice and human AT have revealed vast cell heterogeneity and functionally distinct subtypes that are potential therapeutic targets to metabolic disease. In periparturient dairy cows, AT goes through intensive remodeling and its dysfunction is associated with metabolic disease pathogenesis and decreased productive performance. The contributions of depot-specific cells and subtypes to the development of diseases in dairy cows remain to be studied. Our objective was to elucidate differences in cellular diversity of visceral (VAT) and subcutaneous (SAT) AT in dairy cows at the single-nuclei level. We collected matched SAT and VAT samples from three dairy cows and performed snRNA-seq analysis. We identified distinct cell types including four major mature adipocytes (AD) and three stem and progenitor cells (ASPC) subtypes, along with endothelial cells (EC), mesothelial cells (ME), immune cells, and pericytes and smooth muscle cells. All major cell types were present in both SAT and VAT, although a strong VAT-specificity was observed for ME, which were basically absent in SAT. One ASPC subtype was defined as adipogenic (PPARG+) while the other two had a fibro-adipogenic profile (PDGFRA+). We identified vascular and lymphatic EC subtypes, and different immune cell types and subtypes in both SAT and VAT, i.e., macrophages, monocytes, T cells, and natural killer cells. Not only did VAT show a greater proportion of immune cells, but these visceral immune cells had greater activation of pathways related to immune and inflammatory response, and complement cascade in comparison with SAT. There was a substantial contrast between depots for gene expression of complement cascade, which were greatly expressed by VAT cell subtypes compared to SAT, indicating a pro-inflammatory profile in VAT. Unprecedently, our study demonstrated cell-type and depot-specific heterogeneity in VAT and SAT of dairy cows. A better understanding of depot-specific molecular and cellular features of SAT and VAT will aid in the development of AT-targeted strategies to prevent and treat metabolic disease in dairy cows, especially during the periparturient period.

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F13A1 transglutaminase expression in human adipose tissue increases in acquired excess weight and associates with inflammatory status of adipocytes

Cited by 21 publications

References 64 publications

Interaction between N6-methyladenosine and autophagy in the immune infiltration and subtype classification of thyroid eye disease

Interaction between N6-methyladenosine and autophagy in the immune infiltration and subtype classification of thyroid eye disease

Comprehensive molecular and morphological resolution of blubber stratification in a deep-diving, fasting-adapted seal

Single-nuclei analysis reveals depot-specific transcriptional heterogeneity and depot-specific cell types in adipose tissue of dairy cows

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