Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice
With the gaining prevalence of obesity, related risks during pregnancy are rising. Inflammation and oxidative stress are considered key mechanisms arising in white adipose tissue (WAT) sparking obesity-associated complications and diseases. The established anti-diabetic drug metformin reduces both o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/11/2288 |
| _version_ | 1797492203929468928 |
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| author | Katrin Schmitz Eva-Maria Turnwald Tobias Kretschmer Ruth Janoschek Inga Bae-Gartz Kathrin Voßbrecher Merlin D. Kammerer Angela Köninger Alexandra Gellhaus Marion Handwerk Maria Wohlfarth Dirk Gründemann Eva Hucklenbruch-Rother Jörg Dötsch Sarah Appel |
| author_facet | Katrin Schmitz Eva-Maria Turnwald Tobias Kretschmer Ruth Janoschek Inga Bae-Gartz Kathrin Voßbrecher Merlin D. Kammerer Angela Köninger Alexandra Gellhaus Marion Handwerk Maria Wohlfarth Dirk Gründemann Eva Hucklenbruch-Rother Jörg Dötsch Sarah Appel |
| author_sort | Katrin Schmitz |
| collection | DOAJ |
| description | With the gaining prevalence of obesity, related risks during pregnancy are rising. Inflammation and oxidative stress are considered key mechanisms arising in white adipose tissue (WAT) sparking obesity-associated complications and diseases. The established anti-diabetic drug metformin reduces both on a systemic level, but only little is known about such effects on WAT. Because inhibiting these mechanisms in WAT might prevent obesity-related adverse effects, we investigated metformin treatment during pregnancy using a mouse model of diet-induced maternal obesity. After mating, obese mice were randomised to metformin administration. On gestational day G15.5, phenotypic data were collected and perigonadal WAT (pgWAT) morphology and proteome were examined. Metformin treatment reduced weight gain and visceral fat accumulation. We detected downregulation of perilipin-1 as a correlate and observed indications of recovering respiratory capacity and adipocyte metabolism under metformin treatment. By regulating four newly discovered potential adipokines (alpha-1 antitrypsin, Apoa4, Lrg1 and Selenbp1), metformin could mediate anti-diabetic, anti-inflammatory and oxidative stress-modulating effects on local and systemic levels. Our study provides an insight into obesity-specific proteome alterations and shows novel modulating effects of metformin in pgWAT of obese dams. Accordingly, metformin therapy appears suitable to prevent some of obesity’s key mechanisms in WAT. |
| first_indexed | 2024-03-10T00:59:16Z |
| format | Article |
| id | doaj.art-0a0de6fd3df34e0ab3021f7a07044c92 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T00:59:16Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-0a0de6fd3df34e0ab3021f7a07044c922023-11-23T14:36:39ZengMDPI AGNutrients2072-66432022-05-011411228810.3390/nu14112288Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant MiceKatrin Schmitz0Eva-Maria Turnwald1Tobias Kretschmer2Ruth Janoschek3Inga Bae-Gartz4Kathrin Voßbrecher5Merlin D. Kammerer6Angela Köninger7Alexandra Gellhaus8Marion Handwerk9Maria Wohlfarth10Dirk Gründemann11Eva Hucklenbruch-Rother12Jörg Dötsch13Sarah Appel14Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Obstetrics and Gynecology, University of Regensburg, St. Hedwigs Clinic of the Order of St. John, Steinmetzstrasse 1-3, 93049 Regensburg, GermanyDepartment of Gynecology and Obstetrics, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Gleueler Straße 24, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyDepartment of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, GermanyWith the gaining prevalence of obesity, related risks during pregnancy are rising. Inflammation and oxidative stress are considered key mechanisms arising in white adipose tissue (WAT) sparking obesity-associated complications and diseases. The established anti-diabetic drug metformin reduces both on a systemic level, but only little is known about such effects on WAT. Because inhibiting these mechanisms in WAT might prevent obesity-related adverse effects, we investigated metformin treatment during pregnancy using a mouse model of diet-induced maternal obesity. After mating, obese mice were randomised to metformin administration. On gestational day G15.5, phenotypic data were collected and perigonadal WAT (pgWAT) morphology and proteome were examined. Metformin treatment reduced weight gain and visceral fat accumulation. We detected downregulation of perilipin-1 as a correlate and observed indications of recovering respiratory capacity and adipocyte metabolism under metformin treatment. By regulating four newly discovered potential adipokines (alpha-1 antitrypsin, Apoa4, Lrg1 and Selenbp1), metformin could mediate anti-diabetic, anti-inflammatory and oxidative stress-modulating effects on local and systemic levels. Our study provides an insight into obesity-specific proteome alterations and shows novel modulating effects of metformin in pgWAT of obese dams. Accordingly, metformin therapy appears suitable to prevent some of obesity’s key mechanisms in WAT.https://www.mdpi.com/2072-6643/14/11/2288metforminmaternal obesitypregnancy complicationswhite adipose tissueadipokinesinflammation |
| spellingShingle | Katrin Schmitz Eva-Maria Turnwald Tobias Kretschmer Ruth Janoschek Inga Bae-Gartz Kathrin Voßbrecher Merlin D. Kammerer Angela Köninger Alexandra Gellhaus Marion Handwerk Maria Wohlfarth Dirk Gründemann Eva Hucklenbruch-Rother Jörg Dötsch Sarah Appel Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice Nutrients metformin maternal obesity pregnancy complications white adipose tissue adipokines inflammation |
| title | Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice |
| title_full | Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice |
| title_fullStr | Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice |
| title_full_unstemmed | Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice |
| title_short | Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice |
| title_sort | metformin prevents key mechanisms of obesity related complications in visceral white adipose tissue of obese pregnant mice |
| topic | metformin maternal obesity pregnancy complications white adipose tissue adipokines inflammation |
| url | https://www.mdpi.com/2072-6643/14/11/2288 |
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