Interplay between Obesity-Induced Inflammation and cGMP Signaling in White Adipose Tissue

Publication date: 3 January 2017
Source:Cell Reports, Volume 18, Issue 1
Author(s): Abhishek Sanyal, Jennifer Naumann, Linda Sarah Hoffmann, Agnieszka Chabowska-Kita, Anna Ehrlund, Andreas Schlitzer, Peter Arner, Matthias Blüher, Alexander Pfeifer
Current worldwide figures suggest that obesity is pandemic. Understanding the underlying molecular mechanisms would help develop viable anti-obesity therapies. Here, we assess the influence of obesity-induced inflammation on white adipocyte cyclic guanosine monophosphate (cGMP) signaling, which is beneficial for adipocyte differentiation and thermogenesis. We find that murine gonadal and not inguinal fat is prone to obesity-induced inflammation. Correspondingly, the cGMP cascade is dysregulated in gonadal but not in inguinal fat of obese mice. Analysis of two independent human cohorts reveals a defective cGMP pathway only in visceral fat of obese subjects. Congruently, cGMP signaling is dysregulated in tumor necrosis factor α (TNF-α)-treated primary white adipocytes. TNF-α-mediated suppression of sGCβ1 is mediated via NF-κB, whereas PKG is repressed by JNK signaling. Additionally, TNF-α-activated JNK signaling suppresses PPARγ and aP2. Taken together, the intensity of obesity-induced inflammation dictates the amplitude of cGMP signaling dysregulation in white adipocytes through distinct pathways.

Graphical abstract

Teaser

Sanyal et al. report that the dysregulation of cGMP signaling in adipose tissue of obese mice is proportional to the degree of metaflammation through distinct pathways. Since targeting cGMP signaling ameliorates obesity and associated co-morbidities, knowledge gained from this study suggests avenues for therapy.


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iAqY2e
via IFTTT