The PPARG (peroxisome proliferator-activated receptor gamma) gene has been associated with obesity, metabolic syndrome, and risk for type-2 diabetes. This gene is involved in the regulation of fatty acid storage and in glucose metabolism.

PPAR-gamma is activated by omega-6 polyunsaturated fatty acids and regulates adipocyte differentiation. More specifically, PPARG is a nuclear transcription factor that involved in our natural circadian rhythm, regulating genes involved in storing fat and insulin sensitivity over a 24-hour cycle.[ref]

PPARG could be thought of as a gateway that activates a fat cell to store more fatty acids. It is activated by omega-6 fats, causing fat cells to take fatty acids out of circulation and store them. This then causes cells in the body to take up glucose (mainly from carbohydrates) and use it for energy. This is the way our metabolism normally works- if glucose is available it is used first for energy with fat being stored to be used later when glucose isn’t available.

One type of diabetes drug, thiazolidinediones or TZD’s, works by binding to PPARG, causing the fat cells to take up all available fatty acids and subsequently making the rest of the cells in the body take in more glucose for energy. This does cause blood glucose levels to decrease, but a very common side effect is weight gain.

The most commonly studied variant, rs1801282 or Pro12Ala, is thought to decrease PPARG activity, protecting against weight gain for some.[ref]  But it is conversely associated with obesity in certain populations, probably based on fat intake and type of fat that is common in their diet. A study found that those carrying the G allele were more likely to be obese with a diet higher in saturated fat, while those with the G allele were not at a higher risk for obesity if their fat intake was based more on polyunsaturated fats.[ref] This makes sense when you think about it. In those with the PPARG variant, the body isn’t getting the normal signal from polyunsaturated fatty acids that should make the fat cells fatter.

A mouse study that bred mice to have the rs1801282 variant (Ala) confirmed some of the human studies and explains the differences seen in people who eat different diets.  The mice with the variant, when fed normal chow, were a little bit leaner, had better glucose tolerance and lived a little longer. They also were a little more active in the evening, thus possibly expending a little more energy while eating the same amount of food.  When those same mice with the variant were fed high-fat chow, the mice with the variants became fatter than the mice without the variant. [ref]

Genetic variants:

Check your 23andMe results for rs1801282 (v.4 and v.5):

  • GG: higher risk of obesity with more saturated fat in diet [ref][ref]
  • CG: higher risk of obesity with more saturated fat in diet
  • CC: normal fat metabolism

Lifehacks:

Diet: For those with the PPARG rs1801282 variant, sticking to a diet lower in saturated fat should be protective against weight gain.  (This may be more important in those eating a normal diet with a mixture of fats, carbs, and protein, rather than for someone on a ketogenic diet.)

Block light at night: Focusing on the circadian rhythm function of the gene, it is important to block blue light in the evening from screens and CFL/LED bulbs. You can use blue blocking glasses at night if you don’t want to go back to the age of candles and firelight.  One study showed that sleep duration and risk of T2D is modified by the rs1801282 variant; if you are pre-diabetic, it may be even more important to block blue light in the evening and get good sleep.

Cinnamon: A component of cinnamon, cinnamaldehyde, activates PPARG.[ref] This may be how it helps to lower blood glucose levels (but in a slightly different way than thiazolidinediones, T2D medication).

For the rest of the population without the PPARG variant (CC for rs1801282), decreasing PPARG levels a little may help with weight loss while on a lower omega-6 fat diet. [ref]

  • MCT oil: While poly-unsaturated fats in general bind to PPARG, stimulating uptake of fatty acids into fat cells, one type of medium chain triglycerides may act in a different way. A study showed that decanoic acid (DA), a 10 carbon medium chain triglyceride, binds to PPARG in a different way and specifically does not cause an increase in fat cells. This study (on animals) found that DA decreased blood glucose levels without causing weight gain. One source of DA is Bulletproof’s XCT oil, which contains medium chain triglycerides with both 8 carbons and 10 carbons.
  • Citrus Bergamot: A new study found that citrus bergamot extract could suppress adipogenesis (creation of fat cells) through decreasing PPARG.[ref]
  • Exercise: High-intensity interval training (HIIT) decreases PPAR-gamma levels [ref]
  • Adaptagen: Rhodiola rosea downregulates PPARG [ref]
  • Vitamin: Nicotinic acid (niacinamide, B3) reduces PPARG in response to hypoxia [ref]  interesting study…
  • Astaxanthin is a PPAR – alpha agonist and PPAR-gamma antagonist which led to reduced lipid accumulation in liver cells [ref]  I’m not sure if it would decrease body fat but decreased liver fat should help the liver function better.

More to read:

 

updated 5/18


2 Comments

Luigi · April 24, 2018 at 6:44 pm

I am really sorry I do not understand; rs1801282 is actually Pro12Ala and not Pro72Ala. Moreover, the CC variant is actually the higher risk one as far as the information I found. Can you please explain?

    Debbie Moon · April 24, 2018 at 8:14 pm

    Hi Luigi,
    Thanks for catching the typo on Pro12Ala and letting me know about.
    As far as CC being the higher risk variant, it depends on the studies that you are looking at and the diet of the participants. Keep in mind that the CC genotype is the normal type that is found in about 80% of the population. So a study showing that GG reduces the risk of obesity in people on a Mediterranean diet might list C as the higher risk (compared to G). But with the GG genotype only being found in less than 5% of people, I think it is much more accurate to say that GG is protective (based on diet) and that the CC genotype is normal.
    Here is the snpedia.com page with links to a bunch of studies on this gene (https://www.snpedia.com/index.php/Rs1801282) and you can also do a search in pubmed.gov. If you want to post a link to the studies that show CC (the normal type) as a ‘risk’ for something, I would be happy to read through them and comment.
    Debbie

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