Losing weight is tough, but keeping it off? Even tougher. Fat cells retain a ‘memory’ of obesity through gene changes, making weight regain likely.

People struggle with losing weight and maintaining it. Even after diets, exercise or medical procedures like weight-loss surgery, the pounds often come back. Why is it so difficult to maintain weight loss? Scientists have recently found that fat or adipose tissue has a memory that does not disappear after losing weight (1^✔ ✔Trusted Source
Adipose tissue retains an epigenetic memory of obesity after weight loss

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The memory of the fat tissue explains why it is difficult to stay slim and can pave the way for new treatments for obesity in future.
The body has a way of remembering past obesity even after weight loss. The fat memory is not about the brain but the fat cells have this memory. It involves changes in how the genes respond. These changes are known as epigenetic changes or yo-yo effects.

During obesity, some genes in fat cells make fat storage easier. Even after substantial weight loss, the changes in the fat cells persist. The transcriptional and epigenetic alteration in the fat cells disrupt normal metabolic functions making it easier for individuals to regain lost weight.

Changes in Fat Cells After Weight Loss

Both humans and mice were studied to understand how fat cells behave after weight loss. The study found the following changes:

Transcriptional Changes Persist

The study found that after bariatric surgery, which induces significant weight loss, adipose tissue samples from humans still exhibited transcriptional changes (gene activity changes) linked to their previous obesity.

In both human and mouse models, the transcriptional signatures of obesity—particularly in fat cells—were retained, even two years after the weight loss.

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Epigenetic Modifications in Adipocytes

At the molecular level, obesity induces epigenetic changes (gene behavior change) in the chromatin structure of adipocytes, which remain even after the fat mass is reduced. These modifications—such as changes in histone acetylation and DNA methylation—impair the cell’s normal function and response to metabolic stimuli.

Impaired Adipocyte Function

Adipocytes from previously obese mice showed persistent downregulation of genes responsible for proper fat metabolism, such as those involved in adipogenesis (the process of fat cell creation), fatty acid oxidation, and lipid synthesis. Simultaneously, genes related to inflammation and fibrosis were more active, highlighting a shift toward pathological cell behavior.

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Accelerated Rebound Weight Gain

When the mice were re-exposed to a high-fat diet, those with an epigenetic memory of obesity regained weight more quickly compared to control mice. The epigenetic modifications in adipose tissue “prime” the fat cells to respond in a way that promotes fat storage and metabolic dysfunction, which could explain the rapid weight regain seen in humans after dieting.

Clinical Implications for Weight Loss Management

The findings have significant clinical applications. Weight loss interventions, including bariatric surgery and dietary regimens, may not fully resolve the underlying molecular changes that contribute to obesity. These epigenetic modifications could be why individuals find it difficult to maintain weight loss and why they are at higher risk for developing obesity again.

The discovery of epigenetic memory in adipose tissue opens up exciting new possibilities for improving weight loss results. Rather than focusing only on calorie restriction or fat burning, future therapies could aim to target the epigenetic changes that underlie the body’s resistance to maintaining a lower weight.

Reference:

1. Adipose tissue retains an epigenetic memory of obesity after weight loss – (https://www.nature.com/articles/s41586-024-08165-7)

Source-Medindia