PMID- 31798902
OWN - NLM
STAT- MEDLINE
DCOM- 20200910
LR  - 20200910
IS  - 2052-4897 (Electronic)
IS  - 2052-4897 (Linking)
VI  - 7
IP  - 1
DP  - 2019
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.
PG  - e000776
LID - 10.1136/bmjdrc-2019-000776 [doi]
LID - e000776
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.
CI  - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Hong, Eun Shil
AU  - Hong ES
AD  - Research Institute of Medical Science, Konkuk University School of Medicine, 
      Seoul, South Korea.
AD  - Internal Medicine, Konkuk University Chungju Hospital, Chungju, South Korea.
FAU - Lim, Cheong
AU  - Lim C
AD  - Thoracic and Cardiovascular Surgery, Seoul National University College of 
      Medicine, Seoul, South Korea.
AD  - Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, 
      Seongnam, South Korea.
FAU - Choi, Hye Yeon
AU  - Choi HY
AD  - Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South 
      Korea.
FAU - Lee, Yun Kyung
AU  - Lee YK
AD  - Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South 
      Korea.
FAU - Ku, Eu Jeong
AU  - Ku EJ
AUID- ORCID: 0000-0001-5533-4989
AD  - Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea.
FAU - Moon, Jae Hoon
AU  - Moon JH
AD  - Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South 
      Korea.
AD  - Internal Medicine, Seoul National University College of Medicine, Seoul, South 
      Korea.
FAU - Park, Kyong Soo
AU  - Park KS
AD  - Internal Medicine, Seoul National University College of Medicine, Seoul, South 
      Korea.
FAU - Jang, Hak Chul
AU  - Jang HC
AUID- ORCID: 0000-0002-4188-6536
AD  - Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South 
      Korea.
AD  - Internal Medicine, Seoul National University College of Medicine, Seoul, South 
      Korea.
FAU - Choi, Sung Hee
AU  - Choi SH
AUID- ORCID: 0000-0003-0740-8116
AD  - Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South 
      Korea.
AD  - Internal Medicine, Seoul National University College of Medicine, Seoul, South 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191117
PL  - England
TA  - BMJ Open Diabetes Res Care
JT  - BMJ open diabetes research & care
JID - 101641391
RN  - 0 (Biomarkers)
RN  - 0 (FGF21 protein, human)
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Adipose Tissue/*physiopathology
MH  - Biomarkers/blood
MH  - Body Mass Index
MH  - Case-Control Studies
MH  - China/epidemiology
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/*blood/*epidemiology
MH  - Female
MH  - Fibroblast Growth Factors/*blood
MH  - Follow-Up Studies
MH  - Humans
MH  - Incidence
MH  - Insulin Resistance
MH  - Intra-Abdominal Fat/*physiopathology
MH  - Male
MH  - Middle Aged
MH  - Obesity/*physiopathology
MH  - Prediabetic State/blood/epidemiology
MH  - Prognosis
MH  - Receptors, Fibroblast Growth Factor/*blood
MH  - Signal Transduction
PMC - PMC6861080
OTO - NOTNLM
OT  - adipocytokine
OT  - body fat distribution
OT  - insulin resistance
OT  - type 2 diabetes
COIS- Competing interests: None declared.
EDAT- 2019/12/05 06:00
MHDA- 2020/09/12 06:00
PMCR- 2019/11/17
CRDT- 2019/12/05 06:00
PHST- 2019/07/24 00:00 [received]
PHST- 2019/10/01 00:00 [revised]
PHST- 2019/10/14 00:00 [accepted]
PHST- 2019/12/05 06:00 [entrez]
PHST- 2019/12/05 06:00 [pubmed]
PHST- 2020/09/12 06:00 [medline]
PHST- 2019/11/17 00:00 [pmc-release]
AID - bmjdrc-2019-000776 [pii]
AID - 10.1136/bmjdrc-2019-000776 [doi]
PST - epublish
SO  - BMJ Open Diabetes Res Care. 2019 Nov 17;7(1):e000776. doi: 
      10.1136/bmjdrc-2019-000776. eCollection 2019.