One thing that predisposes individuals who are obese to type 2 diabetes is the persistent, low-level inflammation that results, in part, from dysregulation of the function of white fat tissue in the abdominal cavity between the internal organs (visceral white fat tissue).
New insight into the signaling pathways that contribute to visceral white fat tissue dysregulation has now been provided by Philippe Lefebvre and colleagues, at INSERM, UMR1011, France, who determined that the PPAR-gamma signaling pathway operates differently in the visceral white fat tissue of lean and obese mice and humans. Specifically, it shows increased sensitivity to activation by the anti-diabetic drug rosiglitazone in obese mice and humans.
These data therefore provide a mechanistic explanation why rosiglitazone acts differently in lean and obese patients.
The research appears in the Journal of Clinical Investigation.
- Bruno Lefebvre, Yacir Benomar, Aurore Guιdin, Audrey Langlois, Nathalie Hennuyer, Julie Dumont, Emmanuel Bouchaert, Catherine Dacquet, Luc Pιnicaud, Louis Casteilla, Francois Pattou, Alain Ktorza, Bart Staels, and Philippe Lefebvre. Proteasomal degradation of retinoid X receptor α reprograms transcriptional activity of PPARγ in obese mice and humans. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI38606
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