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Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis

Dixon, Laura J ; Flask, Chris A ; Papouchado, Bettina G ; Feldstein, Ariel E ; Nagy, Laura E Rodriguez-Ortigosa, Carlos M.

PloS one, 2013-02, Vol.8 (2), p.e56100-e56100 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis
Autor: Dixon, Laura J ; Flask, Chris A ; Papouchado, Bettina G ; Feldstein, Ariel E ; Nagy, Laura E
Rodriguez-Ortigosa, Carlos M.
Assuntos: Adiposity ; Animals ; Apoptosis ; Biology ; Biomarkers - metabolism ; Caspase ; Caspase 1 - deficiency ; Caspase 1 - genetics ; Caspase 1 - metabolism ; Caspase-1 ; Chemokines ; Cholesterol ; Cytokines ; Development and progression ; Diet ; Diet, High-Fat - adverse effects ; Enzymes ; Fatty acids ; Fatty liver ; Fatty Liver - enzymology ; Fatty Liver - etiology ; Fatty Liver - genetics ; Fatty Liver - pathology ; Fibrosis ; Gastroenterology ; Gene expression ; Gene Expression Regulation, Enzymologic ; Gene Knockout Techniques ; Genes ; Hepatology ; High fat diet ; House mouse ; Hypotheses ; IL-1β ; Inflammasomes ; Inflammation ; Insulin resistance ; Interleukin-1beta - genetics ; Lipids ; Lipogenesis ; Liver ; Liver - metabolism ; Liver - pathology ; Liver cancer ; Liver diseases ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; Monocyte chemoattractant protein 1 ; Obesity ; Obesity - enzymology ; Obesity - etiology ; Obesity - genetics ; Obesity - pathology ; Oxidation ; Pathogenesis ; Physiology ; Proteins ; RNA ; Rodents ; Steatosis ; Weight control
É parte de: PloS one, 2013-02, Vol.8 (2), p.e56100-e56100
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: LJD LEN AEF. Performed the experiments: LJD BPG CAF. Analyzed the data: LJD LEN. Contributed reagents/materials/analysis tools: LEN AEF. Wrote the paper: LJD LEN AEF.
Descrição: Nonalcoholic steatohepatitis (NASH) is associated with caspase activation. However, a role for pro-inflammatory caspases or inflammasomes has not been explored in diet-induced liver injury. Our aims were to examine the role of caspase-1 in high fat-induced NASH. C57BL/6 wild-type and caspase 1-knockout (Casp1(-/-)) mice were placed on a 12-week high fat diet. Wild-type mice on the high fat diet increased hepatic expression of pro-caspase-1 and IL-1β. Both wild-type and Casp1(-/-) mice on the high fat diet gained more weight than mice on a control diet. Hepatic steatosis and TG levels were increased in wild-type mice on high fat diet, but were attenuated in the absence of caspase-1. Plasma cholesterol and free fatty acids were elevated in wild-type, but not Casp1(-/-) mice, on high fat diet. ALT levels were elevated in both wild-type and Casp1(-/-) mice on high fat diet compared to control. Hepatic mRNA expression for genes associated with lipogenesis was lower in Casp1(-/-) mice on high fat diet compared to wild-type mice on high fat diet, while genes associated with fatty acid oxidation were not affected by diet or genotype. Hepatic Tnfα and Mcp-1 mRNA expression was increased in wild-type mice on high fat diet, but not in Casp1(-/-) mice on high fat diet. αSMA positive cells, Sirius red staining, and Col1α1 mRNA were increased in wild-type mice on high fat diet compared to control. Deficiency of caspase-1 prevented those increases. In summary, the absence of caspase-1 ameliorates the injurious effects of high fat diet-induced obesity on the liver. Specifically, mice deficient in caspase-1 are protected from high fat-induced hepatic steatosis, inflammation and early fibrogenesis. These data point to the inflammasome as an important therapeutic target for NASH.
Editor: United States: Public Library of Science
Idioma: Inglês

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Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis

Dixon, Laura J ; Flask, Chris A ; Papouchado, Bettina G ; Feldstein, Ariel E ; Nagy, Laura E Rodriguez-Ortigosa, Carlos M.

United States: Public Library of Science

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