Weight Loss Genetics – PLIN1

The perilipin 1 gene codes for the protein that covers lipid droplets in fat cells.  This coating protects the lipid droplets from the enzymes that break down fats for use as energy in the body.  Increased perilipin is associated with obesity.  Mice bred to be deficient in perilipin eat more than wild-type mice but gain half the fat weight.  [ref]

“Expression of the perilipin gene is regulated primarily by peroxisome proliferator-activated receptor gamma (PPARγ); however, recent reports also implicate the estrogen receptor-related receptor alpha (ERRα)” [ref]

PLIN1 Genetic Variants:

rs894160 (T is the minor allele, 23andMe orientation)

  • This variant has been associated in some populations, especially Asian,  with obesity and type-2 diabetes. [ref]  [ref]
  • Studies in other populations, including European,  have found little association with obesity. [ref] [ref]
  • The minor allele was associated with a smaller reduction in waist circumference in a study of obese women on a 12-week low-calorie diet.  [ref]
  • One study that may tie together the differences in whether this variant is associated with obesity was done in 2009.  It found that for those with the variant (T allele), low intake of complex carbohydrates led to increased waist circumference compared to those without the T allele.  The opposite was also found in that high intake of complex carbohydrates led to a lower waist circumference compared to those with the wild-type.  Note that this is for complex carbohydrates and the same did not hold true for total carbohydrates (which included sugar and starch).  [ref]

rs2289487 (C is the minor allele)

  • In a trial involving the timing of food intake, carriers of the C allele responded with better weight loss when eating earlier in the day.
  • Other studies have found the C allele to be linked to a lower risk of obesity.

Possible weight loss strategies for PLIN1 variants:

Increased complex carbohydrates but without increased total carbs seems like it should help.  Eating more vegetables, whole grains, and beans would increase complex carbs while cutting down on refined grains and sugar would keep the total carb load down.

A study laid out how exactly perilipin works to control lipolysis (breakdown of fats for energy).  Phosphorylation of perilipin changes the coating of the fat molecules and allows enzymes access to break down the fat for energy.  The pathway goes as follows:  “Catecholamines bind β-adrenergic receptors, which signal through a heterotrimeric G-protein to activate adenyl cyclase, thereby elevating cAMP levels and activating PKA. This step takes place in seconds or faster. PKA phosphorylates both perilipin A and HSL. Maximal phosphorylation of perilipin A takes place in less than 2 minutes,” [ref]



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. 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.