Faculty of Medicine (Division of Experimental Medicine), McGill University, Montreal, QC, Canada.
Faculty of Dentistry (Biomedical Sciences), McGill University, Montreal, QC, Canada.
Int J Obes (Lond). 2021 Mar;45(3):577-587. doi: 10.1038/s41366-020-00722-0. Epub 2020 Nov 21.
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.
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.
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.
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.
F13A1/FXIII-A 转谷氨酰胺酶已与细胞中的脂肪生成以及人与小鼠的肥胖有关，然而，其在人类获得性超重中的作用及其相关分子途径尚未得到探索。
我们检查了 F13A1 的表达，并在体重不同的同卵双胞胎（体重差异（ΔWeight，n=12 为 16.8kg±7.16）中检查了其与人类体重增加的关联。对双胞胎进行了身体成分（通过双能 X 射线吸收法）、腹部体脂肪分布（通过磁共振成像）、肝脂肪含量（通过磁共振波谱）、循环脂肪细胞因子、瘦素和脂联素以及血清脂质的检查。从皮下腹部脂肪组织活检的脂肪组织和脂肪细胞富集部分进行了 Affymetrix 全转录组 mRNA 分析。检查了重和轻的同卵双胞胎之间 F13A1 的差异表达，并对同卵双胞胎之间的 F13A1 差异表达与其相关的转录组变化进行了分析。
F13A1 mRNA 在脂肪组织（p<0.0001）和脂肪细胞富集部分（p=0.0012）中均显著增加。脂肪组织中 F13A1 的差异表达（重与轻的同卵双胞胎之间的 ΔF13A1）与循环脂联素呈显著负相关（p=0.0195），与 ΔWeight（p=0.034）、ΔBodyFat（0.044）和 ΔAdipocyte size（体积，p=0.012）呈正相关；在脂肪细胞富集部分。对 ΔF13A1 与体重相关的 ΔTranscriptome 进行全转录组关联研究（TWAS），鉴定出 182 个与 F13A1 相关的基因（r>0.7，p=0.05），这些基因具有多种生物学途径的功能，包括细胞应激、炎症反应、细胞/白细胞激活、血管生成和细胞外基质重塑。F13A1 与肝脂肪堆积无关。
脂肪组织中 F13A1 水平随获得性超重而增加，并与促炎、细胞应激和组织重塑途径相关。这支持了它在肥胖症中脂肪组织扩张和炎症中的作用。
