Reference Number: 680
Year: 2023
Link: Link to original paper
Health: Cardiometabolic diseases | Cholesterol
Nutrition: Choline
Summary
ABSTRACT: Locating on endoplasmic reticulum and mitochondria associated membrane, Phosphatidylethan olamine N-methyltransferase (PEMT), catalyzes phosphatidylethanolamine methylation to phosphatidylcholine. As the only endogenous pathway for choline biosynthesis in mammals, the dysregulation of PEMT can lead to imbalance of phospholipid metabolism. Dysregulation of phospholipid metabolism in the liver or heart can lead to deposition of toxic lipid species that adversely result in dysfunction of hepatocyte/cardiomyocyte. Studies have shown that PEMT-/- mice increased susceptibility of diet-induced fatty liver and steatohepatitis. However, knockout of PEMT protects against diet-induced atherosclerosis, diet-induced obesity, and insulin resistance. Thus, novel insights to the function of PEMT in various organs should be summarized. Here, we reviewed the structural and functional properties of PEMT, highlighting its role in the pathogenesis of obesity, liver diseases, cardiovascular diseases, and other conditions.
Summary of Findings
This paper explains what the PEMT enzyme does in the body, why it matters for liver health, cholesterol handling, and metabolic disease, and how genetic variants in the PEMT gene can increase a person’s vulnerability to liver fat accumulation and other metabolic problems. It brings together evidence from human studies, animal models, and biochemical research to show how PEMT sits at the centre of several essential metabolic pathways.
PEMT’s main job is to convert phosphatidylethanolamine (PE) into phosphatidylcholine (PC) inside liver cells. PC is a crucial building block for cell membranes, but it also has a special role in packaging fats into VLDL particles, which the liver uses to export triglycerides and cholesterol into the bloodstream. When PEMT activity is low, the liver cannot make enough PC, and this leads to a bottleneck: VLDL particles cannot form properly, so fats build up inside the liver. This is one of the key mechanisms behind non?alcoholic fatty liver disease (NAFLD).
The paper highlights that PEMT is influenced by both diet and hormones. When dietary choline is low, the body relies more heavily on PEMT to make PC internally. But PEMT activity itself depends on methylation, which requires nutrients like folate, B12, and betaine. This means that people with low intake of these nutrients may struggle to maintain adequate PC production. The paper also explains that oestrogen strongly increases PEMT activity, which is why premenopausal women are naturally more protected against choline deficiency and fatty liver than men or postmenopausal women.
A major focus of the review is genetic variation in the PEMT gene, especially common SNPs such as rs7946 and rs12325817. These variants reduce the stability or expression of the PEMT enzyme, lowering the body’s ability to make PC. People with these variants are more likely to develop fatty liver, especially when their diet is low in choline or methyl donors. The paper emphasises that these genetic differences help explain why some individuals develop NAFLD even with a normal body weight or healthy lifestyle.
The authors also discuss PEMT’s role in other diseases. Reduced PEMT activity has been linked to cardiovascular disease, because impaired VLDL secretion alters cholesterol transport. There is also emerging evidence that PEMT may influence insulin resistance, inflammation, and cell stress, making it relevant to broader metabolic health.
Overall, the paper argues that PEMT is a key metabolic enzyme whose function depends on a combination of genetics, diet, and hormonal status. Understanding a person’s PEMT genotype and nutritional environment could help identify those at higher risk of fatty liver and metabolic disease, and guide more personalised dietary strategies, especially around choline and methyl?donor nutrients.
Significance to the Baker
Understanding the role of PEMT and phosphatidylcholine gives a baker a practical advantage when creating food for people dealing with cardiovascular disease, insulin resistance, inflammation, or cellular stress as well as NAFLD. These conditions are all made worse when the liver struggles to export fats properly, something that happens when phosphatidylcholine is low. By choosing ingredients naturally rich in choline, betaine, and methyl donor nutrients, a baker can support healthier fat metabolism and reduce the burden on the liver. Ingredients such as eggs, soy flour, sesame or flax seeds, legumes, and whole grains help maintain the phosphatidylcholine needed for normal VLDL export, which in turn supports healthier cholesterol handling and reduces liver driven inflammation. This means bread can become an everyday tool for supporting metabolic resilience and reducing stress on the body’s cells. Think about seeded sourdough crackers or flatbreads, beetroot enhanced bakes and diversity flours with chickpea, lentil or beans as flours or inclusions in a wholegrain fermented porridge.
