Targeting fibrinogen-like protein 1 is a novel therapeutic strategy to combat obesity

Hung Tsung Wu, Szu Chi Chen, Kang Chih Fan, Chun Heng Kuo, Shin Yu Lin, Shu Huei Wang, Chih Jen Chang, Hung Yuan Li

Research output: Contribution to journalArticle

Abstract

Fibrinogen-like-protein 1 (FGL1) is a novel hepatokine that plays an important role in hepatic steatosis and insulin resistance. Although FGL1 expression can be detected in adipose tissues, the functions of FGL1 in adipose tissues are still unknown. In this study, 356 participants with (body mass index (BMI) ≥25 kg/m2; n = 134) or without obesity (BMI <25 kg/m2; n = 222) were recruited, and we found that the plasma FGL1 concentrations were significantly higher in obese group than those of in the normal weight group, and were positively correlated with age, BMI, waist circumference, fat content, plasma glucose at 2 hours during an oral glucose tolerance test, and the insulin sensitivity index. In univariate analyses, BMI, waist circumference, total fat, visceral fat, and subcutaneous fat areas were positively correlated with FGL1 levels. After adjusting for age and gender, obesity indices, including the BMI and different fat areas, remained significantly associated with FGL1 levels. In order to investigate the causal relationship between FGL1 and obesity, animal and cell models were used. Overexpression of FGL1 in epididymal adipose tissue by lentiviral vector encoding FGL1 increased the fat pad size, whereas FGL1-knockdown by lentiviral vector encoding short-hairpin RNA targeted to FGL1 decreased high-fat diet-induced adiposity. In addition, 3T3-L1 adipocytes were used to clarify the possible mechanism of FGL1-induced adipogenesis. FGL1 induced adipogenesis through an ERK1/2-C/EBPβ-dependent pathway in 3T3-L1 adipocytes. These findings highlight the pathophysiological role of FGL1 in obesity, and FGL1 might be a novel therapeutic target to combat obesity.

Original languageEnglish
Pages (from-to)2958-2967
Number of pages10
JournalFASEB Journal
Volume34
Issue number2
DOIs
Publication statusPublished - Feb 1 2020

Keywords

  • adipogenesis
  • adipokine
  • fibrinogen-like protein-1
  • hepassocin
  • obesity

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Wu, H. T., Chen, S. C., Fan, K. C., Kuo, C. H., Lin, S. Y., Wang, S. H., Chang, C. J., & Li, H. Y. (2020). Targeting fibrinogen-like protein 1 is a novel therapeutic strategy to combat obesity. FASEB Journal, 34(2), 2958-2967. https://doi.org/10.1096/fj.201901925R