A study in the FASEB Journal looked at the interaction between polyunsaturated fat and the Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-α (PPARGC1A) gene. The study found that those with the minor allele (C) of rs4235308 combined with a lower PUFA (polyunsaturated fatty acids) to saturated fat ratio cut their risk of type 2 diabetes almost in half.
So what is PPARGC1A? It is the gene that codes for the PGC-1a protein, which regulates mitochondrial biogenesis (creation). The creation of more mitochondria impacts metabolism through the usage of more energy in brown (thermally active) fat. This protein is the link between external stimuli such as cold temperature and the increase in mitochondria in brown fat, and it links exercise to an increase in mitochondria in muscle. [ref]
Check your genetic data for rs4235308 (23andMe v4, v5;; AncestryDNA)
- C/C: significantly reduced risk of type 2 diabetes with low PUFA diet
- C/T: reduced risk of type 2 diabetes with low PUFA diet
- T/T: typical
A previous study that included PPARGC1A rs4235308 had shown a difference in risk for type 2 diabetes when segregated by population. In Haitian Americans, the SNP was protective against T2D, but in African Americans, it doubled their risk of T2D.[ref] This leads to a question of whether the difference in genetic risk is due is the cultural difference in food choices and PUFA vs. saturated fat ratios.
So how does polyunsaturated fat vs monounsaturated fat fit into the picture?
A monounsaturated fatty acid (oleic acid) was found to activate PGC-1a by inducing deacetylation. The study found “these results indicate that oleic acid, but not other long-chain fatty acids, specifically induces PGC1α deacetylation in skeletal muscle cells through SIRT1”.
Another study looking at the role of PGC-1a in mitochondrial biogenesis summed up the general role of fatty acids: “Recently, a link has been established between elevated fatty acids in muscle and DNA methyltransferase 3B (DNMT3B)–mediated methylation of PGC-1α promoter, leading to its repression with a subsequent reduction in mitochondrial biogenesis”.
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Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.