Challenges in Maintaining Weight Loss Due to Fat Cells' 'Obesity Memory'

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Certain genetic alterations in fat cells persist even after weight loss.
A recent study has revealed something fascinating about our fat tissue. When you look at a scanning electron microscope image of fat cells, they appear rounded and are connected by strands of connective tissue, shown in vibrant red and yellow color. This research suggests that adipose tissue, which is made up of these fat cells, can actually hold onto a genetic "memory" of obesity. This memory might make it more challenging for people to maintain their weight loss after shedding pounds.


Fat tissue may commit weight to memory

For those with obesity, losing weight can reduce the risk of health issues like type 2 diabetes or heart disease. Which is all well and good, as is: keeping the weight off once it’s lost  but for everyone serious about doing so, why do we find this so darn hard? Mice and human cell studies suggest that the battle could be partly due to lasting genetic changes after weight loss.

Epigenetics, or the chemical tags on DNA that function as genetic switchboards, regulate which genes are turned up and down. Now scientists report in Nature on November 18 that a form of DNA tagging that some genes have in fat tissue appears to establish this sort of cellular "memory"  apparently maintaining the effects of obesity. The findings suggest that particular memories may inhibit metabolism and accelerate nutrient absorption, making weight loss resistant to the lasting effects of food.

The results give a clue to the cause of the "yo-yo" syndrome in which people repeatedly shed and then pile on pounds, says Ferdinand von Meyenn, an epigeneticist at ETH Zurich. “How can we improve that? How can we change that? Otherwise the genetic changes will be like oh man how do you come back from this,' he said.
 Von Meyenn and colleagues compared adipose tissue a type of connective tissue that contains fat cells as well as many other types of cells from healthy individuals to patients with obesity. Tissue from people with obesity was less active in genes associated with metabolism, even after those individuals had lost weight.




Researchers have found something intriguing: fat cells from mice that used to be obese take in nutrients much more quickly than those from lean mice. After losing weight, the mice with this "obesity memory" tend to gain weight back faster. 

While losing weight can lead to improvements in metabolic health, the lasting changes in gene expression mean that for some people, keeping the weight off can be really tough, as von Meyenn points out. Even individuals taking weight loss and diabetes medications like Ozempic can regain weight if they stop using them, suggesting that these treatments don’t change the genetic factors at play. However, there’s hope that new drugs or a combination of treatments might one day help erase these memories in fat cells..





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