Relation between lipogranuloma formation and fibrosis, and the origin of brown pigments in lipogranuloma of the canine liver

Lipogranulomas were detected histopathologically in 23 (44.2%) of the 52 liver samples. No significant correlation was found between the density of lipogranulomas and distribution of collagen type I/III in the liver. Pigmentation of lipogranulomas showed significant correlations with that on both hepatocytes and sinusoidal cells, indicating that pigments of lipogranuloma (hemosiderin and ceroid) might be derived from hepatocytes and Kupffer cells.Lipogranulomas are not a contributing factor in hepatic fibrosis, but might be a potential indicator of the accumulation of iron and lipid inside the liver.Lipogranulomas, also termed fatty cysts, are often found in the hepatic parenchyma of dogs [1,2], especially of those with portosystemic shunt (PSS) [3-6], and are defined as lesions consisting of small round cells which contain lipid vacuoles and brown pigments in their cytoplasm, although the amounts of vacuoles and pigments vary among lesions. Besides the canine liver, lipogranulomas are observed in the rat as well as in human livers with cirrhosis [7-10], and are considered to be involved in hepatic cirrhosis in human medicine [9,10]. However, in canine cases, the significance of lipogranulomas in the pathogenesis of cirrhosis is still not clear.Our previous study [11] confirmed that hepatic lipogranuloma consisted of Kupffer cells and/or macrophages, and the cytoplasmic brown pigments were hemosiderin and ceroid, although the pathogenesis of canine lipogranuloma remains unclear. Kupffer cells (resident macrophages) play a key role in hepatic fibrogenesis due to the production of cytokines including transforming growth factor-β (TGF-β) [12-14]. TGF-β, one of the most pro-fibrotic cytokines, is necessary and sufficient for the induction and progression of fibrotic lesions, and may serve as the initiating event in the activation of myofibroblasts, which then secrete a large amount of extracellular matrix [15]. We therefore supposed that the component cells of lipogranu