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
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...
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| Format: | Article |
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BMJ Publishing Group
2019-05-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/7/1/e000776.full |
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| author | Eun Shil Hong Cheong Lim Hye Yeon Choi Yun Kyung Lee Eu Jeong Ku Jae Hoon Moon Kyong Soo Park Hak Chul Jang Sung Hee Choi |
| author_facet | Eun Shil Hong Cheong Lim Hye Yeon Choi Yun Kyung Lee Eu Jeong Ku Jae Hoon Moon Kyong Soo Park Hak Chul Jang Sung Hee Choi |
| author_sort | Eun Shil Hong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-383d8e261aaa48c8a3a3f5ffa77249cc |
| institution | OA Journals |
| issn | 2052-4897 |
| language | English |
| publishDate | 2019-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-383d8e261aaa48c8a3a3f5ffa77249cc2025-08-20T02:37:55ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972019-05-017110.1136/bmjdrc-2019-000776Plasma 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 diabetesEun Shil Hong0Cheong Lim1Hye Yeon Choi2Yun Kyung Lee3Eu Jeong Ku4Jae Hoon Moon5Kyong Soo Park6Hak Chul Jang7Sung Hee Choi8Internal Medicine, Konkuk University Chungju Hospital, Chungju, South KoreaThoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, South KoreaInternal Medicine, Seoul National University Bundang Hospital, Seongnam, South KoreaInternal Medicine, Seoul National University Bundang Hospital, Seongnam, South KoreaInternal Medicine, Chungbuk National University Hospital, Cheongju, Korea (the Republic of)Internal Medicine, Seoul National University College of Medicine, Seoul, South KoreaInternal Medicine, Seoul National University College of Medicine, Seoul, South KoreaDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (the Republic of)Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USABackground 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.https://drc.bmj.com/content/7/1/e000776.full |
| spellingShingle | Eun Shil Hong Cheong Lim Hye Yeon Choi Yun Kyung Lee Eu Jeong Ku Jae Hoon Moon Kyong Soo Park Hak Chul Jang Sung Hee Choi 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 BMJ Open Diabetes Research & Care |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://drc.bmj.com/content/7/1/e000776.full |
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