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


CONCLUSIONS
The monocyte chemoattractant protein-1 secreted by adipose tissue may induce steatosis not only recruiting macrophages but also acting directly on hepatocytes.
Division of Clinical Pathology, Geneva University Hospital, University of Geneva, Geneva, Switzerland.
Sophie
S
Clément
Cristiana
C
Juge-Aubry
Antonino
A
Sgroi
Stéphanie
S
Conzelmann
Valerio
V
Pazienza
Brigitte
B
Pittet-Cuenod
Christoph A
CA
Meier
Francesco
F
Negro
D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism* / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism
D001055:Apolipoproteins B; C111835:CCL2 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D048049:Extracellular Signal-Regulated MAP Kinases; D010729:Phosphoenolpyruvate Carboxykinase (GTP)