Objective: F13A1/FXIII-A transglutaminase has been linked to adipogenesis in cells and to obesity in humans and mice, however, its role and associated molecular pathways in human acquired excess weight have not been explored.
Methods: We examined F13A1 expression and association to human weight gain in weight-discordant monozygotic twins (Heavy-Lean difference (ΔWeight, 16.8 kg ± 7.16 for n = 12). The twin pairs were examined for body composition (by dual-energy X-ray absorptiometry), abdominal body fat distribution (by magnetic resonance imaging), liver fat content (by magnetic resonance spectroscopy), circulating adipocytokines, leptin and adiponectin, as well as serum lipids. Affymetrix full transcriptome mRNA analysis was performed from adipose tissue and adipocyte-enriched fractions from subcutaneous abdominal adipose tissue biopsies. F13A1 differential expression between the heavy and lean co-twins was examined and its correlation transcriptome changes between co-twins were performed.
Results: F13A1 mRNA showed significant increase in adipose tissue (p < 0.0001) and an adipocyte-enriched fraction (p = 0.0012) of the heavier co-twin. F13A1 differential expression in adipose tissue (Heavy-Lean ΔF13A1) showed significant negative correlation with circulating adiponectin (p = 0.0195) and a positive correlation with ΔWeight (p = 0.034), ΔBodyFat (0.044) and ΔAdipocyte size (volume, p = 0.012;) in adipocyte-enriched fraction. A whole transcriptome-wide association study (TWAS) on ΔF13A1 vs weight-correlated ΔTranscriptome identified 182 F13A1-associated genes (r > 0.7, p = 0.05) with functions in several biological pathways including cell stress, inflammatory response, activation of cells/leukocytes, angiogenesis and extracellular matrix remodeling. F13A1 did not associate with liver fat accumulation.
Conclusions: F13A1 levels in adipose tissue increase with acquired excess weight and associate with pro-inflammatory, cell stress and tissue remodeling pathways. This supports its role in expansion and inflammation of adipose tissue in obesity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41366-020-00722-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clearing the path for whole-mount labeling and quantification of neuron- and vessel-density in adipose tissue.
J Cell Sci
January 2025
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
White adipose tissue (WAT) comprises a plethora of cell types beyond adipocytes forming a regulatory network that ensures systemic energy homeostasis. Intertissue communication is facilitated by metabolites and signaling molecules that are spread by vasculature and nerves. Previous works indicated that WAT responds to environmental cues by adapting the abundance of these "communication routes", however, high intra-tissue heterogeneity questions the informative value of bulk or single cell analyses and underscores the necessity of whole-mount imaging.
View Article and Find Full Text PDFAdipo-on-chip: a microphysiological system to culture human mesenchymal stem cells with improved adipogenic differentiation.
In Vitro Model
December 2024
Laboratório de Biologia Básica de Células-Tronco, FIOCRUZ, Rua Professor Algacyr Munhoz Mader, 3775, Instituto Carlos Chagas, Curitiba, Paraná PR 81350-010 Brazil.
Obesity is associated with several comorbidities that cause high mortality rates worldwide. Thus, the study of adipose tissue (AT) has become a target of high interest because of its crucial contribution to many metabolic diseases and metabolizing potential. However, many AT-related physiological, pathophysiological, and toxicological mechanisms in humans are still poorly understood, mainly due to the use of non-human animal models.
View Article and Find Full Text PDFEffects of different pre-conditioning exercise on leptin synthesis and its downstream signalling pathway in T2DM rats.
Iran J Basic Med Sci
January 2025
School of Physical Education, Department of Sports Health, Central China Normal University, Wuhan, 430079, China.
Objectives: This study aimed to evaluate the effects of pre-conditioning exercise on body lipid metabolism, leptin secretion, and the downstream pathways at the early stage of type 2 diabetes mellitus (T2DM).
Materials And Methods: The T2DM model was established using an 8-week high-sugar, high-fat diet combined. The T2DM model was established using an 8-week high-sugar, high-fat diet combined with streptozocin (STZ) injection.
Dapagliflozin treatment decreases visceral and subcutaneous adipose tissue: a systematic review and meta-analysis.
Diabetol Int
January 2025
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, 13 Sur 2901 Colonia Volcanes, 72420 Puebla, Puebla México.
Aims: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been shown to reduce visceral (VAT) and subcutaneous (SAT) adipose tissue. Although many systematic reviews have examined SGLT2i's effect on VAT and SAT, a focus analysis of dapagliflozin, one of the more commonly prescribe SGLT2i, has yet to been done. This study aims to determine the effect of dapagliflozin on reducing VAT and SAT in patients with chronic disease.
View Article and Find Full Text PDFTemporal patterns of liver and adipose lipase abundance across the periparturient period in multiparous Holstein dairy cows.
JDS Commun
January 2025
Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706.
Lipases such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) exist in multiple tissue types. In subcutaneous adipose tissue, PNPLA3 was not altered during the periparturient period. Conversely, strong associations between liver PNPLA3 and liver triglyceride content peripartum were identified and confirmed to be causative using knockdown approaches in a primary bovine hepatocyte model.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!