Over the course of thousands of years of evolution, human beings have developed a mechanism to deal with food scarcity. When food is abundant, we eat more, and the extra calories are stored in the form of fat as an energy reserve. When food is limited, we eat less, and our bodies begin to burn stored fat for energy to sustain life. There are about 200 genes known as “thrifty genes” involved in these fat storage and mobilization processes; the PPARγ gene is one of them.
The thrifty genes were previously an evolutionary advantage in helping us deal with adversity. However, in modern times they have become a burden. Because we have near unlimited access to food, we continually build up our fat stores while rarely getting the chance to use them. As a result, many people have become overweight and obese, which in turn has led to a dramatic increase in type 2 diabetes mellitus (T2DM). The PPARγ gene plays a critical role in this process.
PPARγ is one of the three PPAR (peroxisome proliferator-activated receptor) genes in humans. The other two PPARs are PPARα and PPARδ. PPARγ is mainly responsible for converting excess energy into stored fat. PPARα is mainly responsible for burning fat storage to provide energy when it is necessary, and PPARδ promotes fat synthesis in the liver while at the same time promoting fat burning in muscle tissue.
The function of PPARγ is directly tied to the development of T2DM. The majority of people (83-98%) inherited the original form of the PPARγ gene (aka the thrifty gene) which has become a risk variant as a result of excessive calorie (energy) intake in today’s environment. The constant and efficient conversion of excess energy into fat by this thrifty gene increases the release of free fatty acids into tissues which are the primary culprit for insulin resistance. This is why many insulin-sensitizing drugs specifically target PPARγ.
Fortunately, you can reduce your risk for T2DM with the following dietary choices:
- Avoid overeating so your thrifty gene does not have to produce excess stored fat. The HealthWatch 360 iPhone app or Diet and Nutrition Evaluator can assess your energy requirements based on your own personal profile (height, weight, lifestyle, etc.) to give you a good starting point.
- Restrict total dietary fat according to the USDA Dietary Guideline’s recommended range.
- Increase your intake of dietary polyunsaturated fats (PUFA) while limiting your intake of saturated fats (SFA). A higher ratio of PUFA:SFA is associated with a lower body mass index (BMI) and therefore a lower risk for T2DM for risk variant carriers.
As described in the article Energy Storage and the PPAR Genes, the PPARs are master regulators of energy metabolism. Variants of PPARγ, PPARα, and PPARδ are all pharmaceutical drug targets and are involved in the development of many chronic diseases including obesity, T2DM, dyslipidemia and the metabolic syndrome.