People respond differently to calorie-restricted diets due to differences in their epigenetic markers, and measuring these markers before starting a diet may help identify who is most likely to...
Mechanism
Synthesis from 1 study
When you eat less, your fat cells change how they read their genes by adjusting chemical tags that control gene activity. These changes help burn fat better and reduce inflammation, but everyone starts with slightly different tags, so some people’s bodies respond much better than others. This means...
Most probable mechanism
When a person eats fewer calories, their fat cells sense the drop in energy and change how their genes are read by altering chemical tags on DNA and proteins. These changes turn on genes that help burn fat and make energy more efficiently, while turning off genes that cause inflammation and insulin resistance. Because everyone starts with slightly different gene tags, some people’s fat cells respond better to this change than others, making it possible to predict who will benefit most from eating less.
Reduced calorie intake lowers availability of methyl-donor nutrients and alters cellular energy status, decreasing ATP and increasing AMP levels.
Increased AMP levels activate AMPK, which raises NAD+ levels and stimulates SIRT1 deacetylase activity.
SIRT1 and other nutrient-sensing signals reduce DNA methyltransferase activity and alter histone-modifying enzymes, leading to hypomethylation of metabolic gene promoters and decreased repressive histone methylation.
These epigenetic changes increase chromatin accessibility at promoters of genes involved in lipid oxidation, mitochondrial biogenesis, and insulin signaling, while reducing accessibility at inflammatory gene loci.
Altered microRNA expression further enhances lipid catabolism by suppressing inhibitors of fat breakdown and promoting mitochondrial function.
The combined effect improves metabolic flexibility, reduces ectopic fat accumulation, and enhances insulin sensitivity, but the magnitude of change varies based on individual baseline epigenetic states.
Evidence from Studies
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