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PPARG

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Peroxisome proliferator-activated receptor gamma (PPARG) is a protein which regulates the storage of fatty acids and the metabolism of glucose, and is encoded for by the PPARG gene.  PPARG functions by stimulating other genes to increase lipid uptake and stimulate adipogenesis (the process of making new fat cells in the body) in response to a wide variety of metabolic agents including polyunsaturated fats such as arachidonic acid and even tetrahydrocannabinol (THC)1. There are two forms of PPARG, PPARG1 is found in almost all tissues of the body whereas PPARG2 is found mainly in fat tissue and the intestine2.

There is one SNP in PPARG which is associated with poor health outcomes, 68777C>G, where the G allele is potentially associated with an increased risk of cardiovascular disease on a diet high in saturated fat.

68777C>G

Heart Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs1801282 c g 11 Pro Ala

Risk Description

The risk ‘G’ allele of 68777C>G in the PPARG gene has been identified as potentially increasing cardiovascular risk while on a diet high in saturated fat, conversely there may be a beneficial effect when overall fat intake is relatively low. A study in a mouse model demonstrated that when mice consumed a diet in which ~60% of their calories were derived from fats.

Studies in humans later showed that the ratio saturated to unsaturated fats within total dietary fat intake that may act as a better marker. When the U:S ratio was low (<0.33 i.e. more saturated fat in the diet) then cardiovascular risk markers (LDL-C, HDL-C) were increased, as the ratio normalized and more unsaturated fats were incorporated then the risk decreased3,4. However, other studies have proved less conclusive, although there is debate about whether this is a methodological issue, or whether total fat, saturated fat or unsaturated fats are the key target to focus on.

Alongside this increased risk for cardiovascular disease there is also evidence of increased risk for developing type-2-diabetes based on altered glucose metabolism and resulting changes in insulin sensitivity5, an effect which may be driven more strongly by saturated and trans fats.

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Saturated Fat

The risk allele ‘G’ is associated with an increased cardiovascular risk, and also an increaesd risk of developing type-2-diabetes, when dollowing a diet rich in saturated and trans fats, but low in unsaturated equivalents. Carriers should therefore attempt to re-align their fat intake, favoring unsaturated, especially monounsaturated fats, in their diet.

Discuss this information with your doctor before taking any course of action.

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.
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