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 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.

Automated summary

With the increasing prevalence of obesity, the risks associated with pregnancy are also rising. Inflammation and oxidative stress are identified as key mechanisms in white adipose tissue (WAT) that contribute to obesity-associated complications and diseases. The anti-diabetic drug metformin has known systemic effects, but its effects on WAT are not well understood. This study investigated the effects of metformin treatment during pregnancy using a mouse model of diet-induced maternal obesity. The results showed that metformin treatment reduced weight gain and visceral fat accumulation, and regulated several potential adipokines to mediate anti-diabetic, anti-inflammatory, and oxidative stress-modulating effects.