PPARG: A genetic variant that can protect against obesity and type-2 diabetes, but only if you eat the right diet.

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.

What is PPARG?

The PPARG gene codes for a protein that is important in how your body regulates fat storage and your blood glucose metabolism.

PPAR-gamma is activated by omega-6 polyunsaturated fatty acids and regulates adipocyte (fat cell) 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]

As you can see, PPARG is a key factor in metabolism.

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.

Diabetes and PPARG:

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.

PPARG and weight regulation:

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 genetic data for rs1801282 (23andMe v.4, v.5; AncestryDNA):

  • G/G: higher risk of obesity with more saturated fat in diet [ref][ref]
  • C/G: higher risk of obesity with more saturated fat in the diet
  • C/C: typical fat metabolism


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 (C/C for rs1801282), decreasing PPARG levels a little may help with weight loss while on a lower omega-6 fat diet. [ref]

  • MC/T oil: While poly-unsaturated fats in a general bind to PPARG, stimulating the 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 XC/T 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]
  • Adaptogen: 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

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.