Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

Int J Mol Sci. 2020 Nov 5;21(21):8289. doi: 10.3390/ijms21218289.

Abstract

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy-lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy-Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.

Keywords: F131A; Factor XIII-A; adipocyte size; inflammation; obesity; weight gain.

Publication types

  • Twin Study

MeSH terms

  • Adipocytes / immunology
  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Adipose Tissue / immunology*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Adult
  • Body Composition / genetics
  • Factor XIIIa / genetics*
  • Factor XIIIa / metabolism
  • Female
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Gene Expression Profiling
  • Genetic Association Studies
  • Humans
  • Hypertrophy / genetics
  • Immunity / genetics*
  • Male
  • Obesity / genetics*
  • Obesity / immunology
  • Obesity / metabolism
  • Obesity / pathology
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / genetics
  • Transglutaminases / metabolism
  • Transglutaminases / physiology*
  • Twins, Monozygotic / genetics

Substances

  • Factor XIIIa
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins