Haonan Guo, Yingyu Jing, Yifan Zhang, Lin Song, Wenjing Wu, Jingyue Wang, Mengjun Wang, Xinyi Niu, Mingxi Wang, Xingyan Pan, Ting Wang, Wei Cui, Bo Sun, Ning Wang
{"title":"妊娠前使用GLP-1RA通过妊娠期间肝脏分泌的FGF21改善母体脂质代谢。","authors":"Haonan Guo, Yingyu Jing, Yifan Zhang, Lin Song, Wenjing Wu, Jingyue Wang, Mengjun Wang, Xinyi Niu, Mingxi Wang, Xingyan Pan, Ting Wang, Wei Cui, Bo Sun, Ning Wang","doi":"10.1002/oby.24328","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Obesity in women of childbearing age disrupts lipid metabolism in pregnancy. This study aims to evaluate the impact of prepregnancy glucagon-like peptide-1 receptor agonist (GLP-1RA) use on lipid metabolism during pregnancy.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A retrospective case–control study with 42 participants was employed to analyze the impact of prepregnancy GLP-1RA use on lipid metabolism during pregnancy in women with obesity. An animal study involved 60 virgin female Sprague Dawley rats fed a normal diet or a high-fat diet (HFD) for 8 weeks, with the latter diet divided into HFD + saline, HFD + liraglutide, and HFD + semaglutide for 4 weeks. Rats were mated and then sacrificed on gestational day 21.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Clinically, prepregnancy GLP-1RA use reduced prepregnancy BMI, gestational weight gain, ratio with first-trimester metabolic dysfunction-associated steatotic liver disease, and triglyceride levels during pregnancy. In animals, GLP-1RA improved plasma fibroblast growth factor 21 (FGF21), adiponectin, triglyceride levels, and leptin in midgestation. During late gestation, compared with the HFD group, the GLP-1RA groups exhibited improved liver lipid deposition, increased fatty acid oxidation and lipolysis genes, decreased lipogenesis genes, and increased extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor γ (PPAR-γ) and AMP-activated protein kinase (AMPK)/NAD-dependent protein deacetylase sirtuin-1 (SIRT1) pathways in liver; in the visceral adipose, the GLP-1RA groups showed increased lipolysis genes, decreased lipogenesis genes, and increased phosphorylated to total fibroblast growth factor receptor 1 (FGFR1) with activated ERK/PPAR-γ pathways.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Prepregnancy GLP-1RA use improves maternal lipid metabolism during pregnancy, potentially involving elevated liver-secreted FGF21. This study offers a new strategy for treating lipid metabolic disorders in pregnancy.</p>\n </section>\n </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 8","pages":"1504-1517"},"PeriodicalIF":4.7000,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prepregnancy GLP-1RA use improves maternal lipid metabolism via liver-secreted FGF21 during pregnancy in HFD-fed dams\",\"authors\":\"Haonan Guo, Yingyu Jing, Yifan Zhang, Lin Song, Wenjing Wu, Jingyue Wang, Mengjun Wang, Xinyi Niu, Mingxi Wang, Xingyan Pan, Ting Wang, Wei Cui, Bo Sun, Ning Wang\",\"doi\":\"10.1002/oby.24328\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Obesity in women of childbearing age disrupts lipid metabolism in pregnancy. This study aims to evaluate the impact of prepregnancy glucagon-like peptide-1 receptor agonist (GLP-1RA) use on lipid metabolism during pregnancy.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>A retrospective case–control study with 42 participants was employed to analyze the impact of prepregnancy GLP-1RA use on lipid metabolism during pregnancy in women with obesity. An animal study involved 60 virgin female Sprague Dawley rats fed a normal diet or a high-fat diet (HFD) for 8 weeks, with the latter diet divided into HFD + saline, HFD + liraglutide, and HFD + semaglutide for 4 weeks. Rats were mated and then sacrificed on gestational day 21.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Clinically, prepregnancy GLP-1RA use reduced prepregnancy BMI, gestational weight gain, ratio with first-trimester metabolic dysfunction-associated steatotic liver disease, and triglyceride levels during pregnancy. In animals, GLP-1RA improved plasma fibroblast growth factor 21 (FGF21), adiponectin, triglyceride levels, and leptin in midgestation. During late gestation, compared with the HFD group, the GLP-1RA groups exhibited improved liver lipid deposition, increased fatty acid oxidation and lipolysis genes, decreased lipogenesis genes, and increased extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor γ (PPAR-γ) and AMP-activated protein kinase (AMPK)/NAD-dependent protein deacetylase sirtuin-1 (SIRT1) pathways in liver; in the visceral adipose, the GLP-1RA groups showed increased lipolysis genes, decreased lipogenesis genes, and increased phosphorylated to total fibroblast growth factor receptor 1 (FGFR1) with activated ERK/PPAR-γ pathways.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Prepregnancy GLP-1RA use improves maternal lipid metabolism during pregnancy, potentially involving elevated liver-secreted FGF21. This study offers a new strategy for treating lipid metabolic disorders in pregnancy.</p>\\n </section>\\n </div>\",\"PeriodicalId\":215,\"journal\":{\"name\":\"Obesity\",\"volume\":\"33 8\",\"pages\":\"1504-1517\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Obesity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/oby.24328\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Obesity","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/oby.24328","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Prepregnancy GLP-1RA use improves maternal lipid metabolism via liver-secreted FGF21 during pregnancy in HFD-fed dams
Objective
Obesity in women of childbearing age disrupts lipid metabolism in pregnancy. This study aims to evaluate the impact of prepregnancy glucagon-like peptide-1 receptor agonist (GLP-1RA) use on lipid metabolism during pregnancy.
Methods
A retrospective case–control study with 42 participants was employed to analyze the impact of prepregnancy GLP-1RA use on lipid metabolism during pregnancy in women with obesity. An animal study involved 60 virgin female Sprague Dawley rats fed a normal diet or a high-fat diet (HFD) for 8 weeks, with the latter diet divided into HFD + saline, HFD + liraglutide, and HFD + semaglutide for 4 weeks. Rats were mated and then sacrificed on gestational day 21.
Results
Clinically, prepregnancy GLP-1RA use reduced prepregnancy BMI, gestational weight gain, ratio with first-trimester metabolic dysfunction-associated steatotic liver disease, and triglyceride levels during pregnancy. In animals, GLP-1RA improved plasma fibroblast growth factor 21 (FGF21), adiponectin, triglyceride levels, and leptin in midgestation. During late gestation, compared with the HFD group, the GLP-1RA groups exhibited improved liver lipid deposition, increased fatty acid oxidation and lipolysis genes, decreased lipogenesis genes, and increased extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor γ (PPAR-γ) and AMP-activated protein kinase (AMPK)/NAD-dependent protein deacetylase sirtuin-1 (SIRT1) pathways in liver; in the visceral adipose, the GLP-1RA groups showed increased lipolysis genes, decreased lipogenesis genes, and increased phosphorylated to total fibroblast growth factor receptor 1 (FGFR1) with activated ERK/PPAR-γ pathways.
Conclusions
Prepregnancy GLP-1RA use improves maternal lipid metabolism during pregnancy, potentially involving elevated liver-secreted FGF21. This study offers a new strategy for treating lipid metabolic disorders in pregnancy.
期刊介绍：
Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.
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