Metformin Prevents Key Mechanisms of Obesity-Related Complications in Visceral White Adipose Tissue of Obese Pregnant Mice
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
Affiliations
Katrin Schmitz
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Eva-Maria Turnwald
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Tobias Kretschmer
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Ruth Janoschek
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Inga Bae-Gartz
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Kathrin Voßbrecher
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Merlin D. Kammerer
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Angela Köninger
Department of Obstetrics and Gynecology, University of Regensburg, St. Hedwigs Clinic of the Order of St. John, Steinmetzstrasse 1-3, 93049 Regensburg, Germany
Alexandra Gellhaus
Department of Gynecology and Obstetrics, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany
Marion Handwerk
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Maria Wohlfarth
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Dirk Gründemann
Department of Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany
Eva Hucklenbruch-Rother
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Jörg Dötsch
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
Sarah Appel
Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 16, 50931 Cologne, Germany
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.