Monocyte chemoattractant protein-1 secreted by adipose tissue induces direct lipid accumulation in hepatocytes

Autor: Valerio Pazienza, Christoph A. Meier, Sophie Clément, Stéphanie Conzelmann, Cristiana E. Juge-Aubry, Antonino Sgroi, Brigitte Pittet-Cuénod, Francesco Negro
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Male
medicine.medical_specialty
Chemokine
Carcinoma
Hepatocellular
Adipose Tissue
White/metabolism
Adipose Tissue
White
Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors
Adipose tissue
White adipose tissue
Biology
Fatty Liver/metabolism/pathology
Phosphoenolpyruvate Carboxykinase (GTP)/metabolism
Culture Media
Conditioned/pharmacology
Paracrine signalling
Mice
Chemokine CCL2/metabolism/pharmacology
Internal medicine
Cell Line
Tumor
medicine
Animals
Humans
Secretion
Extracellular Signal-Regulated MAP Kinases
Chemokine CCL2
Cells
Cultured
Apolipoproteins B
ddc:616
Hepatology
Monocyte
Liver Neoplasms
Lipid Metabolism/drug effects/physiology
medicine.disease
Lipid Metabolism
Carcinoma
Hepatocellular/metabolism/pathology
Hepatocytes/drug effects/metabolism
Apolipoproteins B/metabolism
Fatty Liver
Mice
Inbred C57BL
medicine.anatomical_structure
Endocrinology
Hepatocyte
Culture Media
Conditioned
biology.protein
Hepatocytes
Phosphoenolpyruvate Carboxykinase (GTP)
Steatosis
Liver Neoplasms/metabolism/pathology
Zdroj: Hepatology, Vol. 48, No 3 (2008) pp. 799-807
ISSN: 1527-3350
Popis: For many years, adipose tissue has been mainly considered as an inert reservoir for storing triglycerides. Since the discovery that adipocytes may secrete a variety of bioactive molecules (hormones, chemokines, and cytokines), an endocrine and paracrine role for white adipose tissue (WAT) in the regulation of energy balance and other physiological processes has been established, particularly with regard to brain and muscle. In contrast, little is known about the interactions of WAT with liver. Hence, we examined the effect of the secretory products of WAT on hepatocytes. Conditioned medium of human WAT explants induced significant steatosis in hepatocyte cell lines. Factor(s) responsible for the conditioned medium-induced steatosis were screened by a battery of blocking antibodies against different cytokines/chemokines shown to be secreted by WAT. In contrast to interleukin-8 and interleukin-6, the monocyte chemoattractant protein-1 was capable of inducing steatosis in hepatocytes in a time-dependent manner at concentrations similar to those found in conditioned medium. Incubation of conditioned medium with antimonocyte chemoattractant protein-1 antibodies prevented triglyceride accumulation. Investigation of the mechanism leading to the triglyceride accumulation showed that both a diminution of apolipoprotein B secretion and an increase in phosphoenolpyruvate carboxykinase messenger RNA may be involved. Conclusion: The monocyte chemoattractant protein-1 secreted by adipose tissue may induce steatosis not only recruiting macrophages but also acting directly on hepatocytes. (HEPATOLOGY 2008.)
Databáze: OpenAIRE
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