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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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Autores principales: Schmitz, Katrin, Turnwald, Eva-Maria, Kretschmer, Tobias, Janoschek, Ruth, Bae-Gartz, Inga, Voßbrecher, Kathrin, Kammerer, Merlin D., Köninger, Angela, Gellhaus, Alexandra, Handwerk, Marion, Wohlfarth, Maria, Gründemann, Dirk, Hucklenbruch-Rother, Eva, Dötsch, Jörg, Appel, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182976/
https://www.ncbi.nlm.nih.gov/pubmed/35684088
http://dx.doi.org/10.3390/nu14112288
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author Schmitz, Katrin
Turnwald, Eva-Maria
Kretschmer, Tobias
Janoschek, Ruth
Bae-Gartz, Inga
Voßbrecher, Kathrin
Kammerer, Merlin D.
Köninger, Angela
Gellhaus, Alexandra
Handwerk, Marion
Wohlfarth, Maria
Gründemann, Dirk
Hucklenbruch-Rother, Eva
Dötsch, Jörg
Appel, Sarah
author_facet Schmitz, Katrin
Turnwald, Eva-Maria
Kretschmer, Tobias
Janoschek, Ruth
Bae-Gartz, Inga
Voßbrecher, Kathrin
Kammerer, Merlin D.
Köninger, Angela
Gellhaus, Alexandra
Handwerk, Marion
Wohlfarth, Maria
Gründemann, Dirk
Hucklenbruch-Rother, Eva
Dötsch, Jörg
Appel, Sarah
author_sort Schmitz, Katrin
collection PubMed
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.
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spelling pubmed-91829762022-06-10 Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice Schmitz, Katrin Turnwald, Eva-Maria Kretschmer, Tobias Janoschek, Ruth Bae-Gartz, Inga Voßbrecher, Kathrin Kammerer, Merlin D. Köninger, Angela Gellhaus, Alexandra Handwerk, Marion Wohlfarth, Maria Gründemann, Dirk Hucklenbruch-Rother, Eva Dötsch, Jörg Appel, Sarah Nutrients Article 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. MDPI 2022-05-30 /pmc/articles/PMC9182976/ /pubmed/35684088 http://dx.doi.org/10.3390/nu14112288 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schmitz, Katrin
Turnwald, Eva-Maria
Kretschmer, Tobias
Janoschek, Ruth
Bae-Gartz, Inga
Voßbrecher, Kathrin
Kammerer, Merlin D.
Köninger, Angela
Gellhaus, Alexandra
Handwerk, Marion
Wohlfarth, Maria
Gründemann, Dirk
Hucklenbruch-Rother, Eva
Dötsch, Jörg
Appel, Sarah
Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182976/
https://www.ncbi.nlm.nih.gov/pubmed/35684088
http://dx.doi.org/10.3390/nu14112288
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