Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice
Gastroparesis (Gp) is a multifactorial condition commonly observed in females and is characterized by delayed or rapid gastric emptying (GE). The role of ovarian hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus (T2DM) is completely unknown. The aims of our study are to...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/7/582 |
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| author | Jeremy C. Sprouse Chethan Sampath Pandu R. Gangula |
| author_facet | Jeremy C. Sprouse Chethan Sampath Pandu R. Gangula |
| author_sort | Jeremy C. Sprouse |
| collection | DOAJ |
| description | Gastroparesis (Gp) is a multifactorial condition commonly observed in females and is characterized by delayed or rapid gastric emptying (GE). The role of ovarian hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus (T2DM) is completely unknown. The aims of our study are to investigate whether supplementation of 17β-estradiol (E<sub>2</sub>) or progesterone (P<sub>4</sub>) restores impaired nuclear factor erythroid 2-related factor 2 (Nrf2, an oxidative stress-responsive transcription factor) and nitric oxide (NO)-mediated gastric motility in ovariectomized (OVX) mice consuming a high-fat diet (HFD, a model of T2DM). Groups of OVX+HFD mice were administered daily subcutaneous doses of either E<sub>2</sub> or P<sub>4</sub> for 12 weeks. The effects of E<sub>2</sub> and P<sub>4</sub> on body weight, metabolic homeostasis, solid GE, gastric antrum NO-mediated relaxation, total nitrite levels, neuronal nitric oxide synthase (nNOSα), and its cofactor expression levels were assessed in OVX+HFD mice. HFD exacerbated hyperglycemia and insulinemia while accelerating GE (<i>p</i> < 0.05) in OVX mice. Exogenous E<sub>2</sub>, but not P<sub>4</sub>, attenuated rapid gastric emptying and restored gastric nitrergic relaxation, total nitrite levels, nNOSα, and cofactor expression via normalizing Nrf2-Phase II enzymes, inflammatory response, and mitogen-activated protein kinase (MAPK) protein expression in OVX+HFD mice. We conclude that E<sub>2</sub> is beneficial in normalizing metabolic homeostasis and gastric emptying in obese, diabetic OVX mice consuming a fat-rich diet. |
| first_indexed | 2024-03-10T18:42:58Z |
| format | Article |
| id | doaj.art-ca9e63b5e44a45f18fcf4150780c6688 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T18:42:58Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-ca9e63b5e44a45f18fcf4150780c66882023-11-20T05:45:14ZengMDPI AGAntioxidants2076-39212020-07-019758210.3390/antiox9070582Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized MiceJeremy C. Sprouse0Chethan Sampath1Pandu R. Gangula2School of Graduate Studies, Meharry Medical College, Nashville, TN 37208, USADepartment of ODS & Research, School of Dentistry, Nashville, TN 37208, USADepartment of ODS & Research, School of Dentistry, Nashville, TN 37208, USAGastroparesis (Gp) is a multifactorial condition commonly observed in females and is characterized by delayed or rapid gastric emptying (GE). The role of ovarian hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus (T2DM) is completely unknown. The aims of our study are to investigate whether supplementation of 17β-estradiol (E<sub>2</sub>) or progesterone (P<sub>4</sub>) restores impaired nuclear factor erythroid 2-related factor 2 (Nrf2, an oxidative stress-responsive transcription factor) and nitric oxide (NO)-mediated gastric motility in ovariectomized (OVX) mice consuming a high-fat diet (HFD, a model of T2DM). Groups of OVX+HFD mice were administered daily subcutaneous doses of either E<sub>2</sub> or P<sub>4</sub> for 12 weeks. The effects of E<sub>2</sub> and P<sub>4</sub> on body weight, metabolic homeostasis, solid GE, gastric antrum NO-mediated relaxation, total nitrite levels, neuronal nitric oxide synthase (nNOSα), and its cofactor expression levels were assessed in OVX+HFD mice. HFD exacerbated hyperglycemia and insulinemia while accelerating GE (<i>p</i> < 0.05) in OVX mice. Exogenous E<sub>2</sub>, but not P<sub>4</sub>, attenuated rapid gastric emptying and restored gastric nitrergic relaxation, total nitrite levels, nNOSα, and cofactor expression via normalizing Nrf2-Phase II enzymes, inflammatory response, and mitogen-activated protein kinase (MAPK) protein expression in OVX+HFD mice. We conclude that E<sub>2</sub> is beneficial in normalizing metabolic homeostasis and gastric emptying in obese, diabetic OVX mice consuming a fat-rich diet.https://www.mdpi.com/2076-3921/9/7/582gastroparesisestrogenantioxidantscytokinesprogesteronediabetes |
| spellingShingle | Jeremy C. Sprouse Chethan Sampath Pandu R. Gangula Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice Antioxidants gastroparesis estrogen antioxidants cytokines progesterone diabetes |
| title | Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice |
| title_full | Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice |
| title_fullStr | Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice |
| title_full_unstemmed | Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice |
| title_short | Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice |
| title_sort | supplementation of 17β estradiol normalizes rapid gastric emptying by restoring impaired nrf2 and nnos function in obesity induced diabetic ovariectomized mice |
| topic | gastroparesis estrogen antioxidants cytokines progesterone diabetes |
| url | https://www.mdpi.com/2076-3921/9/7/582 |
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