title: Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.
abstract: 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.
authors: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States of America.
authors: Rebecca E
authors: RE
authors: Ringling
authors: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States of America.
authors: Michelle L
authors: ML
authors: Gastecki
authors: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States of America.
authors: Makenzie L
authors: ML
authors: Woodford
authors: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri, United States of America.
authors: Kelly J
authors: KJ
authors: Lum-Naihe
authors: Department of Nutrition Science, Purdue University, West Lafayette, Indiana, United States of America.
authors: Ryan W
authors: RW
authors: Grant
authors: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States of America.|Department of Medicine, University of Missouri, Columbia, Missouri, United States of America.|Research Service, Harry S Truman Memorial Veterans Affairs Hospital, Columbia, Missouri, United States of America.
authors: Lakshmi
authors: L
authors: Pulakat
authors: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States of America.
authors: Victoria J
authors: VJ
authors: Vieira-Potter
authors: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States of America.|Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States of America.|Department of Child Health, University of Missouri, Columbia, Missouri, United States of America.
authors: Jaume
authors: J
authors: Padilla
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D066273:Diet, Western; D018149:Glucose Intolerance; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics*
chemical_list: D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse