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Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease.

Publication ,  Journal Article
Machado, MV; Michelotti, GA; Jewell, ML; Pereira, TA; Xie, G; Premont, RT; Diehl, AM
Published in: Cell Death Dis
February 18, 2016

Obesity and its resulting metabolic disturbances are major health threats. In response to energy surplus, overtaxed adipocytes release fatty acids and pro-inflammatory factors into the circulation, promoting organ fat accumulation (including nonalcoholic fatty liver disease), insulin resistance and the metabolic syndrome. Recently, caspase-2 was linked to lipoapoptosis, so we hypothesized that caspase-2 might be a critical determinant of metabolic syndrome pathogenesis. Caspase-2-deficient and wild-type mice were fed a Western diet (high-fat diet, enriched with saturated fatty acids and 0.2% cholesterol, supplemented with fructose and glucose in the drinking water) for 16 weeks. Metabolic and hepatic outcomes were evaluated. In vitro studies assessed the role of caspase-2 in adipose tissue proliferative properties and susceptibility for lipoapoptosis. Caspase-2-deficient mice fed a Western diet were protected from abdominal fat deposition, diabetes mellitus, dyslipidemia and hepatic steatosis. Adipose tissue in caspase-2-deficient mice was more proliferative, upregulated mitochondrial uncoupling proteins consistent with browning, and was resistant to cell hypertrophy and cell death. The liver was protected from steatohepatitis through a decrease in circulating fatty acids and more efficient hepatic fat metabolism, and from fibrosis as a consequence of reduced fibrogenic stimuli from fewer lipotoxic hepatocytes. Caspase-2 deficiency protected mice from diet-induced obesity, metabolic syndrome and nonalcoholic fatty liver disease. Further studies are necessary to assess caspase-2 as a therapeutic target for those conditions.

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Published In

Cell Death Dis

DOI

EISSN

2041-4889

Publication Date

February 18, 2016

Volume

7

Issue

2

Start / End Page

e2096

Location

England

Related Subject Headings

  • Obesity
  • Non-alcoholic Fatty Liver Disease
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Metabolic Syndrome
  • Male
  • Lipid Metabolism
  • Disease Models, Animal
  • Caspase 2
 

Citation

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Chicago
ICMJE
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Machado, M. V., Michelotti, G. A., Jewell, M. L., Pereira, T. A., Xie, G., Premont, R. T., & Diehl, A. M. (2016). Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease. Cell Death Dis, 7(2), e2096. https://doi.org/10.1038/cddis.2016.19
Machado, M. V., G. A. Michelotti, M. L. Jewell, T. A. Pereira, G. Xie, R. T. Premont, and A. M. Diehl. “Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease.Cell Death Dis 7, no. 2 (February 18, 2016): e2096. https://doi.org/10.1038/cddis.2016.19.
Machado MV, Michelotti GA, Jewell ML, Pereira TA, Xie G, Premont RT, et al. Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease. Cell Death Dis. 2016 Feb 18;7(2):e2096.
Machado, M. V., et al. “Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease.Cell Death Dis, vol. 7, no. 2, Feb. 2016, p. e2096. Pubmed, doi:10.1038/cddis.2016.19.
Machado MV, Michelotti GA, Jewell ML, Pereira TA, Xie G, Premont RT, Diehl AM. Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease. Cell Death Dis. 2016 Feb 18;7(2):e2096.

Published In

Cell Death Dis

DOI

EISSN

2041-4889

Publication Date

February 18, 2016

Volume

7

Issue

2

Start / End Page

e2096

Location

England

Related Subject Headings

  • Obesity
  • Non-alcoholic Fatty Liver Disease
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Metabolic Syndrome
  • Male
  • Lipid Metabolism
  • Disease Models, Animal
  • Caspase 2