Spontaneous development of hepatosteatosis in perilipin-1 null mice with adipose tissue dysfunction.
Biochim Biophys Acta Mol Cell Biol Lipids
; 1863(2): 212-218, 2018 Feb.
Article
en En
| MEDLINE
| ID: mdl-29191637
ABSTRACT
Fatty liver features triglyceride accumulation in hepatocytes and often occurs with obesity and lipodystrophy in humans. Here, we investigated the mechanism of maladaptive hepatosteatosis with adipose-tissue dysfunction. Perilipin 1 (Plin1) did not exist in hepatocytes but was expressed exclusively in adipocytes as a dual modulator for regulating two principal adipose-tissue functions, triglyceride storage and breakdown. Plin1-/- mice showed decreased fat storage but increased lipolysis and efflux of fatty acids from adipose tissue, and hepatosteatosis spontaneously developed without altered circulating inflammatory adipocytokine levels. Plin1-/- adipose dysfunction impaired insulin sensitivity and hepatic glucose metabolism, which might inhibit gluconeogenesis to produce more intermediates for hepatic lipid synthesis. Indeed, the livers of Plin1-/- mice exhibited upregulated mRNA and protein expression of key enzymes and transcriptional factors for the uptake and transport of fatty acids and for de novo synthesis of triglycerides, but the expression of key enzymes and transcriptional factors for fatty-acid oxidation was downregulated. Biochemical assays in Plin1-/- mice confirmed increased fatty acid synthase activity but decreased activity of mitochondrial carnitine palmitoyltransferase 1 and [3H]-palmitate oxidation in the liver. We concluded that dysregulation of two principal functions, adipose storage and hydrolysis, had deleterious consequences on the hepatic lipid metabolism and thereby caused maladaptive hepatosteatosis. This mouse model might mimic and explain the pathogenesis of hepatosteatosis occurring in two typical disorders of adipose tissue dysfunction, obesity and lipodystrophy, particularly in lipodystrophic patients with Plin1 mutation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tejido Adiposo
/
Hepatocitos
/
Metabolismo de los Lípidos
/
Hígado Graso
/
Perilipina-1
/
Hígado
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Biol Lipids
Año:
2018
Tipo del documento:
Article
País de afiliación:
China