AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is a well-known reproductive syndrome usually associated with obesity, insulin resistance, and hyperinsulinemia. Although the first signs of PCOS begin early in adolescence, it is underexplored whether peripubertal obesity predisposes women to PCOS metabolic disturba...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/16/8942 |
| _version_ | 1797409901203423232 |
|---|---|
| author | Bojana Mićić Ana Teofilović Ana Djordjevic Nataša Veličković Djuro Macut Danijela Vojnović Milutinović |
| author_facet | Bojana Mićić Ana Teofilović Ana Djordjevic Nataša Veličković Djuro Macut Danijela Vojnović Milutinović |
| author_sort | Bojana Mićić |
| collection | DOAJ |
| description | Polycystic ovary syndrome (PCOS) is a well-known reproductive syndrome usually associated with obesity, insulin resistance, and hyperinsulinemia. Although the first signs of PCOS begin early in adolescence, it is underexplored whether peripubertal obesity predisposes women to PCOS metabolic disturbances. To highlight that, we examined the impact of postnatal overfeeding-induced obesity, achieved by litter size reduction during the suckling period, on metabolic disturbances associated with visceral and subcutaneous adipose tissue (VAT and SAT) function in the 5α-dihydrotestosterone (5α-DHT)-induced animal model of PCOS. We analyzed markers of insulin signaling, lipid metabolism, and energy sensing in the VAT and SAT. Our results showed that postnatally overfed DHT-treated Wistar rats had increased VAT mass with hypertrophic adipocytes, together with hyperinsulinemia and increased HOMA index. In the VAT of these animals, insulin signaling remained unchanged while lipogenic markers decreased, which was accompanied by increased AMPK activation. In the SAT of the same animals, markers of lipogenesis and lipolysis increased, while the activity of AMPK decreased. Taken together, obtained results showed that postnatal overfeeding predisposes development of PCOS systemic insulin resistance, most likely as a result of worsened metabolic function of SAT, while VAT preserved its tissue insulin sensitivity through increased activity of AMPK. |
| first_indexed | 2024-03-09T04:21:13Z |
| format | Article |
| id | doaj.art-b7f3dc12bfa349ffa6010029fcd382ae |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:21:13Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b7f3dc12bfa349ffa6010029fcd382ae2023-12-03T13:47:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316894210.3390/ijms23168942AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary SyndromeBojana Mićić0Ana Teofilović1Ana Djordjevic2Nataša Veličković3Djuro Macut4Danijela Vojnović Milutinović5Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd, 11060 Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd, 11060 Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd, 11060 Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd, 11060 Belgrade, SerbiaClinic for Endocrinology, Diabetes and Metabolic Diseases University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Doktora Subotića 13, 11000 Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 142 Despot Stefan Blvd, 11060 Belgrade, SerbiaPolycystic ovary syndrome (PCOS) is a well-known reproductive syndrome usually associated with obesity, insulin resistance, and hyperinsulinemia. Although the first signs of PCOS begin early in adolescence, it is underexplored whether peripubertal obesity predisposes women to PCOS metabolic disturbances. To highlight that, we examined the impact of postnatal overfeeding-induced obesity, achieved by litter size reduction during the suckling period, on metabolic disturbances associated with visceral and subcutaneous adipose tissue (VAT and SAT) function in the 5α-dihydrotestosterone (5α-DHT)-induced animal model of PCOS. We analyzed markers of insulin signaling, lipid metabolism, and energy sensing in the VAT and SAT. Our results showed that postnatally overfed DHT-treated Wistar rats had increased VAT mass with hypertrophic adipocytes, together with hyperinsulinemia and increased HOMA index. In the VAT of these animals, insulin signaling remained unchanged while lipogenic markers decreased, which was accompanied by increased AMPK activation. In the SAT of the same animals, markers of lipogenesis and lipolysis increased, while the activity of AMPK decreased. Taken together, obtained results showed that postnatal overfeeding predisposes development of PCOS systemic insulin resistance, most likely as a result of worsened metabolic function of SAT, while VAT preserved its tissue insulin sensitivity through increased activity of AMPK.https://www.mdpi.com/1422-0067/23/16/8942polycystic ovary syndromeobesityvisceral adipose tissuesubcutaneous adipose tissueinsulin resistance5α-dihydrotestosterone |
| spellingShingle | Bojana Mićić Ana Teofilović Ana Djordjevic Nataša Veličković Djuro Macut Danijela Vojnović Milutinović AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome International Journal of Molecular Sciences polycystic ovary syndrome obesity visceral adipose tissue subcutaneous adipose tissue insulin resistance 5α-dihydrotestosterone |
| title | AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome |
| title_full | AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome |
| title_fullStr | AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome |
| title_full_unstemmed | AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome |
| title_short | AMPK Activation Is Important for the Preservation of Insulin Sensitivity in Visceral, but Not in Subcutaneous Adipose Tissue of Postnatally Overfed Rat Model of Polycystic Ovary Syndrome |
| title_sort | ampk activation is important for the preservation of insulin sensitivity in visceral but not in subcutaneous adipose tissue of postnatally overfed rat model of polycystic ovary syndrome |
| topic | polycystic ovary syndrome obesity visceral adipose tissue subcutaneous adipose tissue insulin resistance 5α-dihydrotestosterone |
| url | https://www.mdpi.com/1422-0067/23/16/8942 |
| work_keys_str_mv | AT bojanamicic ampkactivationisimportantforthepreservationofinsulinsensitivityinvisceralbutnotinsubcutaneousadiposetissueofpostnatallyoverfedratmodelofpolycysticovarysyndrome AT anateofilovic ampkactivationisimportantforthepreservationofinsulinsensitivityinvisceralbutnotinsubcutaneousadiposetissueofpostnatallyoverfedratmodelofpolycysticovarysyndrome AT anadjordjevic ampkactivationisimportantforthepreservationofinsulinsensitivityinvisceralbutnotinsubcutaneousadiposetissueofpostnatallyoverfedratmodelofpolycysticovarysyndrome AT natasavelickovic ampkactivationisimportantforthepreservationofinsulinsensitivityinvisceralbutnotinsubcutaneousadiposetissueofpostnatallyoverfedratmodelofpolycysticovarysyndrome AT djuromacut ampkactivationisimportantforthepreservationofinsulinsensitivityinvisceralbutnotinsubcutaneousadiposetissueofpostnatallyoverfedratmodelofpolycysticovarysyndrome AT danijelavojnovicmilutinovic ampkactivationisimportantforthepreservationofinsulinsensitivityinvisceralbutnotinsubcutaneousadiposetissueofpostnatallyoverfedratmodelofpolycysticovarysyndrome |