Activated hepatic stellate cells (HSCs), the major source of the collagens involved in fibrosis and non-alcoholic fatty liver disease (NAFLD), undergo a profound loss of lipid and vitamin A storage capacity, as a consequence of a decline in expression of ‘adipogenic’ transcription factors such as peroxisome proliferator-activated receptor-¿ (PPAR¿). By contrast, hepatocytes undergo a micro- and macro-vesicular steatosis, reflecting the accumulation of triacylglycerol, and associated with chronic inflammation and fibrosis. These paradoxical findings are extended in this issue: Kang and Chen demonstrate that while low-density lipoproteins (LDL) can activate HSCs, curcumin can inhibit this process by activation of PPAR¿, which not only represses gene expression of SREBP-2 and LDLR, but via induction of expression of SREBP-1c, restores the lipid storage capacity characteristic of quiescent HSCs, suggesting that curcumin may be of therapeutic usage in protecting against liver steatosis and fibrosis.
- lipid metabolism
- liver disease