Squalene: A Trove of Metabolic Actions

Squalene is present in high concentration in the liver of certain sharks and in small concentrations in olive oil. Previous studies showed that its administration decreases hepatic steatosis in male Apoe-knockout mice, but these changes might be complex. Transcriptomics, using DNA microarrays, and proteomics from mitochondrial and microsomal fractions, analyzed by 2D-DIGE and mass spectrometry, were used in these mice that received 1 g/kg/day squalene for 10 weeks. Squalene administration significantly modified the expression of genes such as lipin 1 (Lpin1) and thyroid hormone responsive (Thrsp). Changes in methionine adenosyltransferase 1 alpha (Mat1α), short-chain specific acyl-CoA dehydrogenase (Acads), and thioredoxin domain–containing protein 5 (Txndc5) expressions were consistent with their protein levels. Their mRNA levels were associated with hepatic fat content. These results suggest that squalene action involves changes in hepatic gene expression associated with its anti-steatotic properties. This approach shows new connections between nutrition and gene expression since Txndc5, a gene with unknown biological function, was upregulated by squalene administration. Overall, this nutrigenomic approach illustrates the effects of squalene and provides further support to the idea that not all monounsaturated fatty acid–containing oils behave similarly. Therefore, selection of cultivars producing olive oils enriched in this compound will be a plus.