PT  - JOURNAL ARTICLE
AU  - Eun Shil Hong
AU  - Cheong Lim
AU  - Hye Yeon Choi
AU  - Yun Kyung Lee
AU  - Eu Jeong Ku
AU  - Jae Hoon Moon
AU  - Kyong Soo Park
AU  - Hak Chul Jang
AU  - Sung Hee Choi
TI  - Plasma fibroblast growth factor 21 levels increase with ectopic fat accumulation and its receptor levels are decreased in the visceral fat of patients with type 2 diabetes
AID  - 10.1136/bmjdrc-2019-000776
DP  - 2019 Nov 01
TA  - BMJ Open Diabetes Research & Care
PG  - e000776
VI  - 7
IP  - 1
4099  - http://drc.bmj.com/content/7/1/e000776.short
4100  - http://drc.bmj.com/content/7/1/e000776.full
SO  - BMJ Open Diab Res Care2019 Nov 01; 7
AB  - 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.