In terms of molecular cell biology, the findings indicate the presence of limited, albeit significant, spontaneous lysosomal turnover of α-galactose lipid conjugates demasked by GLA deficiency. Some findings (see above) suggest there might be an inverse relationship between TAG lipid depots and lysosomal storage. This brings to mind an observation in preadipocytes (Novikoff et al.
1980) that showed that the lysosomal system was active in autophagocytosis, which in Fabry disease could represent a source of lipid substrate. Similar activation of the lysosomal system was described in the process of mouse L-cell adipocyte differentiation (Borisov
1982). A similar relationship between physiological lipid storage deposits and the degree of lysosomal expansion in lysosomal storage disorders was described in Ito cells (Elleder
1984; Elleder
2010). Knowledge about adipocyte participation in other lysosomal storage disorders is restricted to neuronal ceroid lipofuscinosis type 2 (Rowan and Lake
1995) and Elleder M (unpublished observations). Our results extend the knowledge of the adipocyte lysosomal system that was directly shown to be active under experimental conditions (Borisov
1982; Meshkinpour et al.
1996). Indirect evidence of its presence stems from several experimental studies (Hou et al.
2009; Kobayashi et al.
1980; Kovsan et al.
2007; Lee and Fried
2006; Palacios et al.
2001; Zvonic et al.
2005). What is really missing is evidence for possible TAG lysosomal turnover in adipocytes. Our unpublished results, limited to several skin biopsies of cholesteryl ester storage disease (CESD), showed no presence of lysosomal storage (unpublished observations). We are not aware of any analogous studies in human cases of Wolman disease. Our observation involving a single case (unpublished) revealed no discernible lysosomal storage in adipocytes (unpublished). This contrasts with the striking impact of acid lipase deficiency on adipose tissue in the mouse model, featured by progressive loss of white adipose tissue and monovacuolar transformation of brown adipose tissue (Du et al.
2001).