PPAR-γ is a nuclear receptor which is activated by fatty acids such as omega 3´s. When activated, it upregulates expression of genes that play a role in lipid and carbohydrate metabolism. This gene is the target for the Type 2 Diabetes drug Thiazolidinedione (TZD) which increases insulin sensitivity and lowers circulating glucose levels. However a common side effect of the drug is weight gain. PPAR-γ is secreted from fat cells most commonly in white adipose tissue.
In this recent study conducted at the Univ of Cincinatti,scientists tried to understand whether it was the brain´s PPAR-γ system that was responsible for the weight gain following TZD treatment and if this system was activated by a high fat diet. To understand the system, they used animal models.
They found that the weight gain was due to the activation of PPAR-γ system in the brain which altered activity in the region of the brain which is associated with appetite. In addition, the same system was activated by a high fat intake and so it seems that activation of this system leads individuals to eat more but also the effect is worse when consuming a high fat diet. The authors concluded that a new type of TZD will need to be designed which maintains its effectiveness in lowering blood glucose, but is not as available to the brain.
Testing for the protective Pro12ALA SNP on the PPAR-γ gene is common in most Nutrigenomic panels. Although it is not a definitive marker of pre-diabetes, it does give an indication of genetic susceptibility to insulin sensitivity.
Karen K Ryan, Bailing Li, Bernadette E Grayson, Emily K Matter, Stephen C Woods, Randy J Seeley. A role for central nervous system PPAR-γ in the regulation of energy balance. Nature Medicine, 2011; DOI: 10.1038/nm.2349