The Differential Expression of Cide Family Members is Associated with Nafld Progression from Steatosis to Steatohepatitis.
Sci Rep
; 9(1): 7501, 2019 05 16.
Article
en En
| MEDLINE
| ID: mdl-31097771
ABSTRACT
Improved understanding of the molecular mechanisms responsible for the progression from a "non-pathogenic" steatotic state to Non-Alcoholic Steatohepatitis is an important clinical requirement. The cell death-inducing DFF45 like effector (CIDE) family members (A, B and FSP27) regulate hepatic lipid homeostasis by controlling lipid droplet growth and/or VLDL production. However, CIDE proteins, particularly FSP27, have a dual role in that they also regulate cell death. We here report that the hepatic expression of CIDEA and FSP27 (α/ß) was similarly upregulated in a dietary mouse model of obesity-mediated hepatic steatosis. In contrast, CIDEA expression decreased, but FSP27-ß expression strongly increased in a dietary mouse model of steatohepatitis. The inverse expression pattern of CIDEA and FSP27ß was amplified with the increasing severity of the liver inflammation and injury. In obese patients, the hepatic CIDEC2 (human homologue of mouse FSP27ß) expression strongly correlated with the NAFLD activity score and liver injury. The hepatic expression of CIDEA tended to increase with obesity, but decreased with NAFLD severity. In hepatic cell lines, the downregulation of FSP27ß resulted in the fractionation of lipid droplets, whereas its overexpression decreased the expression of the anti-apoptotic BCL2 marker. This, in turn, sensitized cells to apoptosis in response to TNF α and saturated fatty acid. Considered together, our animal, human and in vitro studies indicate that differential expression of FSP27ß/CIDEC2 and CIDEA is related to NAFLD progression and liver injury.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Reguladoras de la Apoptosis
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Enfermedad del Hígado Graso no Alcohólico
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia