Article Text
Abstract
Background Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator that has beneficial effects on glucose and lipid metabolism. However, plasma FGF21 levels are paradoxically increased in type 2 diabetes mellitus (T2DM) and obesity, suggesting resistance to this ligand. FGF21 acts mainly on adipose tissue and ectopic fat accumulation is a typical feature in metabolic deterioration such as diabetes, metabolic syndrome, and cardiovascular disease.
Objective To investigate the relationship between FGF21 resistance and ectopic fat accumulation.
Research design and methods Subjects who underwent 64-slice multidetector CT (MDCT) were enrolled (n=190). Plasma FGF21 levels and MDCT data of ectopic fats at various sites were analyzed. Human visceral and subcutaneous fat tissues from abdominal and coronary artery bypass surgery were obtained. FGF21 receptor expression and postreceptor signaling in different fat deposits of both control and T2DM subjects were analyzed.
Results Plasma FGF21 levels were significantly associated with body mass index, triglyceride, homeostatic model assessment of insulin resistance, and Matsuda index. Plasma FGF21 levels were significantly higher in patients with T2DM than in the pre-diabetes and normal glucose tolerance groups. The ectopic fat phenotypes (visceral, epicardial, intrahepatic, and intramuscular fat) of T2DM were significantly higher than controls. Plasma FGF21 levels were elevated and exhibited a strong positive correlation with ectopic fat accumulation in T2DM. The expression of genes comprising the FGF21 signaling pathway was also lower in visceral fat than in subcutaneous fat in this disease.
Conclusions Human FGF21 resistance in T2DM could result from increases in FGF21-resistant ectopic fat accumulation. Our study provides novel clinical evidence linking FGF21 resistance and T2DM pathogenesis.
- insulin resistance
- type 2 diabetes
- adipocytokine
- body fat distribution
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Footnotes
Contributors ESH designed the study, carried out the research, analyzed and interpreted the results, and wrote the manuscript. CL contributed to obtaining tissue samples and for study design. HYC and YKL carried out sample preparation and the laboratory work. EJK, JHM, KSP, and HCJ helped plan the study and data analysis. SHC designed the study, contributed to the clinical research (patient enrollment, sample collection, and data analysis), and reviewed the manuscript.
Funding This study is funded by the National Research Foundation of Korea (NRF-2018R1A5A2024425) to SHC.
Disclaimer The funder had no involvement in study design, analysis of data, writing the report, and publication.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was approved by the local ethics committee (SNUBH IRB number B-1203/147-006, number A111218-CP02) and all subjects provided written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.