Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity
Fibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent DNA demethylation in the mouse liver via peroxisome proliferator-activated receptor (PPAR) α during the fetal to lactation periods...
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| Format: | Article |
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The Japan Endocrine Society
2024-09-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/9/71_EJ23-0570/_html/-char/en |
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| author | Hiroyuki Shinozaki Shiori Kawai Mami Gamo-Kawasaki Ayano Takei Kyoko Tsujikado Kazunori Fukuda Mototaka Yamauchi Kenji Hara Takafumi Tsuchiya Kohzo Takebayashi Koshi Hashimoto |
| author_facet | Hiroyuki Shinozaki Shiori Kawai Mami Gamo-Kawasaki Ayano Takei Kyoko Tsujikado Kazunori Fukuda Mototaka Yamauchi Kenji Hara Takafumi Tsuchiya Kohzo Takebayashi Koshi Hashimoto |
| author_sort | Hiroyuki Shinozaki |
| collection | DOAJ |
| description | Fibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent DNA demethylation in the mouse liver via peroxisome proliferator-activated receptor (PPAR) α during the fetal to lactation periods. Furthermore, we found that the DNA methylation state of Fgf21 was involved in obesity in adult animals. In the present study, we analyzed the DNA methylation state of the FGF21 gene (FGF21) in obese patients using genomic DNA extracted from human monocytes and macrophages and investigated the pathophysiological significance of the FGF21 expression response to pemafibrate (PM), a PPARα ligand. We examined 67 patients with obesity stratified into in- and outpatient cohorts. A positive correlation was observed between serum FGF21 levels and triglyceride (TG) levels before PM administration. However, changes in serum FGF21 levels following PM administration did not correlate with the FGF21 DNA methylation rate, except at one CpG site. The body mass index (BMI) and serum TG levels positively correlated with the FGF21 DNA methylation rate, particularly at different CpG positions. A negative correlation was observed between absolute changes in serum FGF21 levels and the ratio of change in serum TG levels after PM administration. Collectively, these results indicate the potential of FGF21 DNA methylation as a surrogate indicator of BMI and serum TG levels, while absolute changes in serum FGF21 levels after PM administration may offer prognostic insights into the efficacy of reducing serum TG levels through PM administration. |
| format | Article |
| id | doaj-art-43428d5deb89468386f0725b530c53c5 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-43428d5deb89468386f0725b530c53c52025-01-22T05:20:11ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-09-0171990792410.1507/endocrj.EJ23-0570endocrjAnalysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesityHiroyuki Shinozaki0Shiori Kawai1Mami Gamo-Kawasaki2Ayano Takei3Kyoko Tsujikado4Kazunori Fukuda5Mototaka Yamauchi6Kenji Hara7Takafumi Tsuchiya8Kohzo Takebayashi9Koshi Hashimoto10Department of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanDepartment of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanDepartment of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanCollaborative Research Center, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanCollaborative Research Center, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanCollaborative Research Center, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanDepartment of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanDepartment of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanDepartment of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanDepartment of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanDepartment of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama 343-8555, JapanFibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent DNA demethylation in the mouse liver via peroxisome proliferator-activated receptor (PPAR) α during the fetal to lactation periods. Furthermore, we found that the DNA methylation state of Fgf21 was involved in obesity in adult animals. In the present study, we analyzed the DNA methylation state of the FGF21 gene (FGF21) in obese patients using genomic DNA extracted from human monocytes and macrophages and investigated the pathophysiological significance of the FGF21 expression response to pemafibrate (PM), a PPARα ligand. We examined 67 patients with obesity stratified into in- and outpatient cohorts. A positive correlation was observed between serum FGF21 levels and triglyceride (TG) levels before PM administration. However, changes in serum FGF21 levels following PM administration did not correlate with the FGF21 DNA methylation rate, except at one CpG site. The body mass index (BMI) and serum TG levels positively correlated with the FGF21 DNA methylation rate, particularly at different CpG positions. A negative correlation was observed between absolute changes in serum FGF21 levels and the ratio of change in serum TG levels after PM administration. Collectively, these results indicate the potential of FGF21 DNA methylation as a surrogate indicator of BMI and serum TG levels, while absolute changes in serum FGF21 levels after PM administration may offer prognostic insights into the efficacy of reducing serum TG levels through PM administration.https://www.jstage.jst.go.jp/article/endocrj/71/9/71_EJ23-0570/_html/-char/enobesityfibroblast growth factor (fgf) 21dna methylationpemafibrate (pm) |
| spellingShingle | Hiroyuki Shinozaki Shiori Kawai Mami Gamo-Kawasaki Ayano Takei Kyoko Tsujikado Kazunori Fukuda Mototaka Yamauchi Kenji Hara Takafumi Tsuchiya Kohzo Takebayashi Koshi Hashimoto Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity Endocrine Journal obesity fibroblast growth factor (fgf) 21 dna methylation pemafibrate (pm) |
| title | Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity |
| title_full | Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity |
| title_fullStr | Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity |
| title_full_unstemmed | Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity |
| title_short | Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity |
| title_sort | analysis of serum levels and dna methylation of fibroblast growth factor 21 using peripheral blood derived genomes in patients with obesity |
| topic | obesity fibroblast growth factor (fgf) 21 dna methylation pemafibrate (pm) |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/9/71_EJ23-0570/_html/-char/en |
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