|Title:||Targeting fibrinogen-like protein 1 is a novel therapeutic strategy to combat obesity||Authors:||Wu H.-T.
|Issue Date:||2020||Publisher:||John Wiley and Sons Inc.||Journal Volume:||34||Journal Issue:||2||Start page/Pages:||2958-2967||Source:||FASEB Journal||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. ? 2019 Federation of American Societies for Experimental Biology
|ISSN:||0892-6638||DOI:||10.1096/fj.201901925R||metadata.dc.subject.other:||fibrinogen; fibrinogen like protein 1; glucose; mitogen activated protein kinase 3; unclassified drug; FGL1 protein, human; Fgl1 protein, mouse; fibrinogen; small interfering RNA; 3T3-L1 cell line; adult; animal cell; animal tissue; Article; body mass; computer assisted tomography; controlled study; epididymis fat; fat pad; fatty liver; female; glucose blood level; human; insulin resistance; insulin sensitivity; intra-abdominal fat; major clinical study; male; mouse; nonhuman; obesity; priority journal; protein targeting; subcutaneous fat; waist circumference; adipocyte; adipogenesis; adipose tissue; adverse event; animal; fat intake; genetics; MAPK signaling; metabolism; obesity; pathology; pharmacology; 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Animals; Blood Glucose; Dietary Fats; Female; Fibrinogen; Humans; Male; MAP Kinase Signaling System; Mice; Obesity; RNA, Small Interfering
|Appears in Collections:||醫學系|
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