Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications
Maternal high-fat (HF) diet exposure in utero may affect fetal development and cause metabolic problems throughout life due to lipid dysmetabolism and oxidative damage. Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its repro...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/22/14239 |
| _version_ | 1797465063643152384 |
|---|---|
| author | Chien-Fu Huang Mao-Meng Tiao I-Chun Lin Li-Tung Huang Jiunn-Ming Sheen You-Lin Tain Chien-Ning Hsu Ching-Chou Tsai Yu-Ju Lin Hong-Ren Yu |
| author_facet | Chien-Fu Huang Mao-Meng Tiao I-Chun Lin Li-Tung Huang Jiunn-Ming Sheen You-Lin Tain Chien-Ning Hsu Ching-Chou Tsai Yu-Ju Lin Hong-Ren Yu |
| author_sort | Chien-Fu Huang |
| collection | DOAJ |
| description | Maternal high-fat (HF) diet exposure in utero may affect fetal development and cause metabolic problems throughout life due to lipid dysmetabolism and oxidative damage. Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its reprogramming effect on offspring is undetermined. This study assesses the effects of maternal metformin treatment on hepatic steatosis in offspring caused by maternal HF diet. Female rats were fed either a control or an HF diet before conception, with or without metformin treatment during gestation, and placenta and fetal liver tissues were collected. In another experiment, the offspring were fed a control diet until 120 d (adult stage). Metformin treatment during pregnancy ameliorates placental oxidative stress and enhances placental glucose transporter 1 (<i>GLUT1</i>), <i>GLUT3</i>, and <i>GLUT4</i> expression levels through 5’ adenosine monophosphate-activated protein kinase (AMPK) activation. Maternal metformin treatment was shown to reprogram maternal HF diet-induced changes in offspring fatty liver with the effects observed in adulthood as well. Further validation is required to develop maternal metformin therapy for clinical applications. |
| first_indexed | 2024-03-09T18:17:08Z |
| format | Article |
| id | doaj.art-e0f83ee2458c41179f14ce91a2355cc2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:08Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e0f83ee2458c41179f14ce91a2355cc22023-11-24T08:40:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221423910.3390/ijms232214239Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter ModificationsChien-Fu Huang0Mao-Meng Tiao1I-Chun Lin2Li-Tung Huang3Jiunn-Ming Sheen4You-Lin Tain5Chien-Ning Hsu6Ching-Chou Tsai7Yu-Ju Lin8Hong-Ren Yu9Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanMaternal high-fat (HF) diet exposure in utero may affect fetal development and cause metabolic problems throughout life due to lipid dysmetabolism and oxidative damage. Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its reprogramming effect on offspring is undetermined. This study assesses the effects of maternal metformin treatment on hepatic steatosis in offspring caused by maternal HF diet. Female rats were fed either a control or an HF diet before conception, with or without metformin treatment during gestation, and placenta and fetal liver tissues were collected. In another experiment, the offspring were fed a control diet until 120 d (adult stage). Metformin treatment during pregnancy ameliorates placental oxidative stress and enhances placental glucose transporter 1 (<i>GLUT1</i>), <i>GLUT3</i>, and <i>GLUT4</i> expression levels through 5’ adenosine monophosphate-activated protein kinase (AMPK) activation. Maternal metformin treatment was shown to reprogram maternal HF diet-induced changes in offspring fatty liver with the effects observed in adulthood as well. Further validation is required to develop maternal metformin therapy for clinical applications.https://www.mdpi.com/1422-0067/23/22/14239maternal high-fatmetforminplacentasteatosisDOHaD |
| spellingShingle | Chien-Fu Huang Mao-Meng Tiao I-Chun Lin Li-Tung Huang Jiunn-Ming Sheen You-Lin Tain Chien-Ning Hsu Ching-Chou Tsai Yu-Ju Lin Hong-Ren Yu Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications International Journal of Molecular Sciences maternal high-fat metformin placenta steatosis DOHaD |
| title | Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications |
| title_full | Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications |
| title_fullStr | Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications |
| title_full_unstemmed | Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications |
| title_short | Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications |
| title_sort | maternal metformin treatment reprograms maternal high fat diet induced hepatic steatosis in offspring associated with placental glucose transporter modifications |
| topic | maternal high-fat metformin placenta steatosis DOHaD |
| url | https://www.mdpi.com/1422-0067/23/22/14239 |
| work_keys_str_mv | AT chienfuhuang maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT maomengtiao maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT ichunlin maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT litunghuang maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT jiunnmingsheen maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT youlintain maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT chienninghsu maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT chingchoutsai maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT yujulin maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications AT hongrenyu maternalmetformintreatmentreprogramsmaternalhighfatdietinducedhepaticsteatosisinoffspringassociatedwithplacentalglucosetransportermodifications |