It has been suggested that dysregulation of lipid biology may contribute to pathology in neurodegenerative diseases. A new paper now indicates that further study of this possibility would be warranted in Parkinson's disease by showing that the protein Parkin, which is mutated in some people with Parkinson's disease, regulates lipid metabolism.

On the basis of epidemiological evidence and preliminary observations in mice lacking Parkin, Kye-Young Kim et al. (J. Clin. Invest. 121, 3701–3712) hypothesized that Parkin may be involved in the regulation of lipid metabolism. To test this, they compared wild-type and Parkin-knockout mice fed a high-fat diet (HFD) and found that the mice lacking Parkin were resistant to HFD-associated metabolic changes, including weight gain and hepatic insulin resistance. Moreover, the Parkin knockouts did not induce the expression of lipid transport proteins observed in the livers of wild-type mice on an HFD.

By studying hepatocytes overexpressing Parkin as well as mouse cells and cells from people with Parkinson's disease lacking Parkin, the authors showed that, mechanistically, Parkin mediates its effects on fat uptake by stabilizing the lipid transport protein CD36. However, whether defects in lipid metabolism contribute to Parkinson's disease pathogenesis in people with mutations in PARK2, the gene encoding Parkin, remains to be investigated in future studies.