Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance

• Published in: PloS one 2016-09, Vol.11 (9), p.e0161939-e0161939
• Main Authors: Ringling, Rebecca E, Gastecki, Michelle L, Woodford, Makenzie L, Lum-Naihe, Kelly J, Grant, Ryan W, Pulakat, Lakshmi, Vieira-Potter, Victoria J, Padilla, Jaume
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - pathology; Age; Animals; Aorta; Atherosclerosis; Bioindicators; Biology and Life Sciences; Body fat; Cardiomyocytes; Cardiomyopathy; Care and treatment; Caspase; Caspase-1; CCR2 protein; CD11c antigen; Cholesterol; Complications; Complications and side effects; Coronary vessels; Cytokines; Diabetes; Diet; Diet, Western; Ecology and Environmental Sciences; Exercise physiology; Fibrosis; Glucose; Glucose Intolerance; Glucose tolerance; Heart; Heart diseases; Hypertension; Hypertrophy; Inflammasomes; Inflammation; Inflammation - pathology; Interleukin 1; Interleukin 18; Intolerance; Male; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein 1; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; Nutrition research; Obesity; Pathogens; Physical Sciences; Proteins; Rodents; Stiffening; Tumor necrosis factor; Uric acid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161939

We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis.