Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08-22

AUTHORS

Petra Mulder, Martine C. Morrison, Lars Verschuren, Wen Liang, J. Hajo van Bockel, Teake Kooistra, Peter Y. Wielinga, Robert Kleemann

ABSTRACT

Obesity is associated with chronic low-grade inflammation that drives the development of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). We recently showed that white adipose tissue (WAT) constitutes an important source of inflammatory factors. Hence, interventions that attenuate WAT inflammation may reduce NAFLD development. Male LDLr-/- mice were fed a high-fat diet (HFD) for 9 weeks followed by 7 weeks of HFD with or without rosiglitazone. Effects on WAT inflammation and NAFLD development were analyzed using biochemical and (immuno)histochemical techniques, combined with gene expression analyses. Nine weeks of HFD feeding induced obesity and WAT inflammation, which progressed gradually until the end of the study. Rosiglitazone fully blocked progression of WAT inflammation and activated PPARγ significantly in WAT. Rosiglitazone intervention did not activate PPARγ in liver, but improved liver histology and counteracted the expression of genes associated with severe NAFLD in humans. Rosiglitazone reduced expression of pro-inflammatory factors in WAT (TNF-α, leptin) and increased expression of adiponectin, which was reflected in plasma. Furthermore, rosiglitazone lowered circulating levels of pro-inflammatory saturated fatty acids. Together, these observations provide a rationale for the observed indirect hepatoprotective effects and suggest that WAT represents a promising therapeutic target for the treatment of obesity-associated NAFLD. More... »

PAGES

31542

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep31542

DOI

http://dx.doi.org/10.1038/srep31542

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047040401

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27545964


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