The Role Of Amino Acids In Diet, Obesity, & Diabetes (PPM1K)

The PPM1K gene helps create a protein named mitochondrial protein phosphatase 1K [R].

This protein plays an important role in the metabolism of certain amino acids called branched chain amino acids (BCAAs), such as leucine [R].

There’s some evidence that certain genetic variants of PPM1K may impair the body’s ability to metabolize BCAAs, ultimately leading to an increase in BCAA levels [R].

This may be an issue as several studies have linked high BCAA levels to metabolic problems, such as insulin resistance, obesity, and type 2 diabetes [R, R, R].

Research also suggests that certain variants of PPM1K may affect how the body responds to certain diets [R, R].

How Does PPM1K Affect Diet And Blood Glucose?

Studies show that certain genetic variants of PPM1K may have negative effects on the body.

More specifically, research suggests that the ‘C’ allele in rs1440581 may be associated with risk of type 2 diabetes and poor response to certain diets [R, R, R].

According to researchers, this occurs because the ‘C’ allele may impair the body’s ability to metabolize BCAAs, leading to a higher than normal level of BCAAs [R].

High levels of BCAAs in the blood have been strongly linked to insulin resistance and type 2 diabetes in a number of studies [R, R, R].

However, it’s not entirely clear why high BCAA levels have this effect. 

Some researchers suggest that BCAAs may activate the mTOR signaling pathway, which can induce insulin resistance [R].

Research On PPM1K

The POUNDS LOST Trial

Short for “Preventing Overweight Using Novel Dietary Strategies”, the POUNDS LOST trial is a study that followed 734 overweight or obese adults for a 2-year period [R].

During this time, subjects were randomly assigned to 1 of 4 calorie-restricted diets that were either high-fat or low-fat and either high-protein or average-protein [R].

At the end of the trial, researchers found some interesting results.

Subjects who were on the high-fat diet and carried the ‘C’ allele in rs1440581 had less weight loss and smaller improvements to insulin resistance compared to the ‘T’ allele [R].

Participants in the study were predominantly white, but there were also black, Hispanic, and Asian groups included [R].

According to the POUNDS LOST trial, people with the ‘T’ allele in rs1440581 may benefit more from a calorie-restricted high-fat diet in terms of weight loss and insulin sensitivity compared to those without this allele.

The NUGENOB Trial

The NUGENOB trial, which stands for “Nutrient Gene Interactions in Human Obesity”, studied 757 obese adults who were put on a calorie-restricted diet for 10 weeks [R].

Participants were randomly assigned to 2 different controlled diets, a low-fat diet and a high-fat diet [R].

Similar to the POUNDS LOST trial, researchers found that those carrying the ‘C’ allele experienced smaller improvements to weight and insulin resistance while on a calorie-restricted high-fat diet [R].

On the other hand, the ‘C’ allele was associated with better weight loss and insulin resistance improvements for those on the low-fat diet compared to the ‘T’ allele [R].

Subjects in this study were all from European countries, including the United Kingdom, Netherlands, France, Spain, Czech Republic, Sweden, and Denmark [R].

The NUGENOB trial suggests that people carrying the ‘T’ allele in rs1440581 may benefit more from calorie-restricted high-fat diets. On the other hand, those with the ‘C’ allele may benefit more from calorie-restricted low-fat diets in terms of weight loss and improvements to insulin resistance.

Other Studies

One study followed over 6,000 Chinese non-diabetic patients for a 5-year period [R].

For those carrying the ‘C’ allele in rs1440581, an increase in BMI resulted in greater increases in insulin levels and insulin resistance compared to those with the ‘T’ allele [R].

The researchers also found that each ‘C’ allele in rs1440581 is associated with a 20% higher risk of type 2 diabetes [R].

A study of Chinese patients found that the ‘C’ allele in rs1440581 is associated with higher insulin levels, insulin resistance, and risk of type 2 diabetes.

You can see your genotype for PPM1K in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

Primary SNP: 

PPM1K rs1440581

• ‘T’ = Associated with better improvements to weight and insulin sensitivity when consuming a calorie-restricted high-fat diet
• ‘C’ = Associated with better improvements to weight and insulin sensitivity when consuming a calorie-restricted low-fat diet
• The ‘C’ allele is also associated with a higher risk of type 2 diabetes in Chinese populations
• About 19% of all people worldwide have the ‘TT’ genotype
• About 33% of all people worldwide have the ‘CC’ genotype