Weight Loss Yo-Yo Effect Could Be Explained By Fat Cell “Memories”

Weight Loss Yo-Yo Effect Could Be Explained By Fat Cell “Memories”



Fat cell “memory” could help explain why weight loss can be difficult to maintain, according to new research. In experiments using mice and samples of human fat tissue, the scientists found that epigenetic changes persist even after weight loss, in effect meaning that the cells “remember” what it was like to be at a higher weight.

The “yo-yo effect” is well known to many who’ve attempted a weight loss program or used weight loss medications in the past. No matter how positive the initial results, it’s extremely common for people to regain some or all of the weight back quite quickly. While there’s some evidence from research that weight regain doesn’t totally negate the benefits to cardiovascular health, it can still be a disheartening reality for people striving to achieve a weight loss goal.

The new study goes a step towards explaining why this happens by investigating what’s going on inside our fat cells at a molecular level.

Epigenetics is the branch of science that deals with modifications that are added to DNA as a result of environmental or behavioral factors. Rather than altering the actual underlying DNA sequence, epigenetic markers are added (or removed – the process is reversible) to the chromosome at points in the sequence that change how the cell interprets it, and how the resulting protein functions.

In essence, study co-first author Laura Hinte explained to Technology Networks, “Epigenetics tells a cell what kind of cell it is and what it should do.” Importantly for our purposes, epigenetic markers – though theoretically removable – can remain stable for years, and in some cases can be passed on to the next generation.

In their study, the team compared samples of fat tissue from a group of people living with severe obesity and a control group, a total of 23 people. They found that different patterns of gene activation were present in the two groups, which was still the case two years after the participants with obesity had undergone weight loss surgery. Although the participants themselves had much lower body weights by that stage, as far as their fat cells were concerned, nothing had changed.

“These results indicate that obesity induces cellular and transcriptional (obesogenic) changes in the [fat tissue] which are not resolved following significant [weight loss],” the team write in their paper.

To investigate further, they performed experiments on mice. Comparing fat cells from obese mice and from those that had been on a strict diet to lose weight, they again observed that the epigenetic memory persisted after weight loss. When the mice that had lost weight were put back onto a high fat diet, they also gained weight more quickly than control mice.

“The fat cells remember the overweight state and can return to this state more easily,” senior author Ferdinand von Meyenn told Technology Networks. “That means we’ve found a molecular basis for the yo-yo effect.”

What’s not clear yet is for how long this memory might persist, and that’s something that future research will have to explore.

As some other experts in the field who were not directly involved in the study commented to Nature News, this study does not prove causation – we can’t say for absolute certain that the epigenetic modifications directly cause weight regain, nor can we yet pinpoint which specific epigenetic markers are driving the effect. If we could, it might open up the possibility of targeting them with drugs.

For now, one message the researchers want to get across is that this finding helps underscore the fact that weight regain following weight loss should not be deemed a “failure”. Hinte told Nature News, “It means that you need more help, potentially. It’s not your fault.”

The study is published in Nature.



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