Nlrp3 is a key modulator of diet-induced nephropathy and renal cholesterol accumulation

Metabolic syndrome (MetSyn) is a major health concern and associates with the development of kidney disease. The mechanisms linking MetSyn to renal disease have not been fully elucidated but are known to involve hyperuricemia, inflammation, and fibrosis. Since the innate immune receptor Nlrp3 is an...

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Bibliographic Details
Published in:Kidney international Vol. 85; no. 5; pp. 1112 - 1122
Main Authors: Bakker, Pieter J., Butter, Loes M., Kors, Lotte, Teske, Gwendoline J.D., Aten, Jan, Sutterwala, Fayyaz S., Florquin, Sandrine, Leemans, Jaklien C.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.05.2014
Elsevier Limited
Subjects:
Animals
Biomarkers - blood
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cholesterol, Dietary - metabolism
chronic nephropathy
Diet, High-Fat
Diet, Western
Dietary Carbohydrates - metabolism
Disease Models, Animal
dyslipidemia
Fibrosis
Fructose - metabolism
immunology and pathology
Inflammasomes - immunology
Inflammasomes - metabolism
Kidney - immunology
Kidney - metabolism
Kidney - pathology
Kidney Diseases - etiology
Kidney Diseases - genetics
Kidney Diseases - immunology
Kidney Diseases - metabolism
Kidney Diseases - pathology
Macrophages - immunology
Macrophages - metabolism
Male
Metabolic Syndrome - etiology
Metabolic Syndrome - genetics
Metabolic Syndrome - immunology
Metabolic Syndrome - metabolism
Metabolic Syndrome - pathology
Mice, Inbred C57BL
Mice, Knockout
NLR Family, Pyrin Domain-Containing 3 Protein
obesity
Receptors, LDL - metabolism
Signal Transduction
Sterol Regulatory Element Binding Protein 2 - metabolism
immunology and pathology
chronic nephropathy
dyslipidemia
obesity
ISSN:0085-2538, 1523-1755, 1523-1755
Online Access:Get full text
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Summary:Metabolic syndrome (MetSyn) is a major health concern and associates with the development of kidney disease. The mechanisms linking MetSyn to renal disease have not been fully elucidated but are known to involve hyperuricemia, inflammation, and fibrosis. Since the innate immune receptor Nlrp3 is an important mediator of obesity and inflammation, we sought to determine whether Nlrp3 is involved in the development of MetSyn-associated nephropathy by giving wild-type or Nlrp3-knockout mice a Western-style compared to a normal diet or water without or with fructose. A plausible driver of pathology, the Nlrp3-dependent cytokine IL-1β was not increased in the kidney. Interestingly, Nlrp3-dependent renal cholesterol accumulation, another well-known driver of renal pathology, was enhanced during MetSyn. We also determined the role of Nlrp3 and fructose-fortified water on the development of MetSyn and kidney function since fructose is an important driver of obesity and kidney disease. Surprisingly, fructose did not induce MetSyn but, irrespective of this, did induce Nlrp3-dependent renal inflammation. The presence of Nlrp3 was crucial for the development of Western-style diet–induced renal pathology as reflected by the prevention of renal inflammation, fibrosis, steatosis, microalbuminuria, and hyperuricemia in the Nlrp3-knockout mice. Thus, Nlrp3 may mediate renal pathology in the context of diet-induced MetSyn.
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ISSN:0085-2538
1523-1755
1523-1755
DOI:10.1038/ki.2013.503