PPARG variants: saturated fat, obesity, and type 2 diabetes risk

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 specifically 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]

The most commonly studied variant, rs1801282 or Pro72Ala, is thought to decrease PPARG activity, enhance glucose tolerance, and also protect against diabetes.[ref]  But it is also associated with obesity in certain populations, possibly based on fat intake.  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]

Genetic variants:

rs1801282 (G is the minor allele)

  • minor allele is highly protective against heart disease [ref]
  • decrease risk of type-2 diabetes for minor allele [ref]
  • increased risk of obesity with the minor allele [ref] may be only for those on a high-fat diet [ref]
  • minor increased risk of obesity, but still protective against insulin resistance and diabetes [ref]  This study notes that the population (urban) ate a high-fat, refined carb diet.
Check your 23andMe results for rs1801282 (v.4 and v.5):
GG: higher risk of obesity with more saturated fat in diet, decreased risk of heart disease and T2D
CG: higher risk of obesity with more saturated fat in diet, decreased risk of heart disease and T2D
CC: normal

rs1805192 (G is the minor allele)

  • decreased risk of diabetic retinopathy [ref]
  • decreased risk of essential hypertension [ref]

Diet and Lifestyle:

For those with the PPARG rs1801282 variant, sticking to a diet lower in fat should be protective against weight gain.

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 candle and firelight.  One study showed 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.

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

  • A new study found that citrus bergamia (Bergamot) juice could suppress adipogenesis (creation of fat cells) through decreasing PPARG.  [ref]
  • High-intensity interval training decreases PPAR-gamma levels [ref]
  • Rhodiola rosea downregulates PPARG [ref]
  • 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.


updated 1/18

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