Your Fat Cells Harbor a Memory of Being Fat

New Research published yesterday reveals how fat cells retain a memory of obesity after weight loss, and how this could impact your ability to maintain a healthy body composition.

*My Newsletter subscribers get early access to my breakdowns. But there is also now a full video reviewing these data on YouTube if you prefer the video. If you prefer to read, then please continue to scroll.*

New Research published yesterday reveals how fat cells retain a memory of obesity after weight loss, and how this could impact your ability to maintain a healthy body composition.

The paper in question was just published in Nature.

Adipose tissue refers to body fat, and epigenetic memory – well, if you don’t know what that is I’ll explain it momentarily with an analogy. But first, let me provide a framework.

“Yo-yo” diet effect

You’re probably aware of the “yo-yo” diet effect, whereby people who lose excess weight are prone to gain it back.

Think, the Biggest Loser – where people lose a ton of weight quickly… but typically if you follow them up you find their metabolisms slow and the end up gaining most, if not all the weight back.

Bummer.

But is this weight regain phenomenon a purely behavioral phenomenon, or are there deeper metabolic mechanisms at play?

The Data

In this study, researchers took cell samples from human patients who were always lean versus those who had a history of obesity but who had lost weight, and measured gene expression profiles from their fat at the time of surgery and 2 years later after substantial (at least 25% of their body weight) weight loss.

They found significant changes in fat cells (adipocytes), as well as fat cell precursors and also in other cell types, like the endothelial cells that line blood vessels.

Overall, fat cells from individuals with a history of obesity showed down-regulation of genes relates to metabolic functions and up-regulation of genes relates to inflammation functions

The authors write:

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

Fat cells from people who had previously had obesity were less metabolically healthy and more inflammatory.  

NERD ALERT & Mechanistic Tangent

For a quick tangent – and you can skip down to the next section if you don’t want the details – the technique used to measure gene expression profiles in the fat is called single-nucleus RNA sequencing whereby a suspension of cells is broken up and the nuclei of the cells are separated in a centrifuge. You can then sort the types of cell nuclei with something called “Fluorescence-Activated Cell Sorting” where antibodies are used to tag different nuclei from different cell types that permit them to be identified and sorted with a laser based on their fluorescence properties. How cool! Okay, back to what matters more for you…

Back to the Data

To get more granular, the researchers experiments in mice where they fattened some mice using a high-sugar high-fat obesogenic diets, and then normalized their weight through dietary restriction and compared these to mice who never had obesity.

They found, consistent with the human data, persistently gene expression changes, including down-regulation of metabolic pathways, such as fatty acid oxidation, mitochondrial signaling, etc., and up-regulation of inflammatory pathways.

Now, how does it work. What is this epigenetic memory?

An Analogy For Epigenetic Memory

Your genetic code is like a book… even though all cells in your body contain your full genetic code they are different.

Why?

Because in different cells different pages are opened or shut. This determines the fat or function of cells.

What’s more, cells can “bookmark” or dog-ear pages for easy access. In the cell these are “epigenetic” changes, where tags are put on to DNA or the protein complexes around which DNA is wound. This makes it easier (or harder) to access certain pages (certain genes), changing their expression profiles.

Hopefully that makes sense?

And that’s how cells develop a “memory” of past events, including the memory “I was once an ‘obese’ fat cell.”

If it’s not too dark to say, think of it like PTSD for fat cells.

Weight Regain After Weight Loss

Now, are these changes functionally or clinically meaningful? It would appear so. Human observational and clinical data suggest those who have lost weight are more prone to put weight back on.

Although, of course, in free living humans it’s hard to disentangle the effects of behavioral and constitutional (inborn) differences from those imposed from true epigenetic changes brought about by a history of obesity.

However, carefully controlled mouse experiments – which in this case should probably generalize to humans – do indeed strongly suggest that a history of obesity predisposes fat cells to take up sugar more readily, build up fat stores in response to insulin more quickly, and develop fatty liver more easily.

High-Level Take-Aways

Those are the main findings from the paper.

And it’s a bit of a dark story because it suggests having had obesity kind of’ like a “screw you” from biology.

No fair, right!? Well, I have a different take and three concluding thoughts for you.

(1) It’s true that that a history of obesity puts a person behind the metabolic eight-ball.

However, this might not be permanent.

Bear in mind those who had obesity in this study and then ‘recovered’ had a relatively short time frame being newly not obese as compared to the time course over which they initially developed obesity (presumably over decades).

So, what we don’t know but what I suspect is that if someone is able to maintain a lean, healthy weight for enough time… the epigenetic memory may fade. Thus, it’s possible – although not proven – that the longer you can maintain a healthy weight the easier it becomes.

Also, I’d maintain that your present lifestyle choices still do have the dominant effect. Even your road might be rockier, it doesn’t mean you shouldn’t or can’t traverse it.

These data do not say one cannot maintain a lean healthy weight after having obesity… they just acknowledge that biology can be a jerk sometimes.

(2) The epigenetic memory is not specific to fat cells.

There were also changes, for example, in the endothelial cells that line blood vessels. Thus, a history of obesity could predispose individuals to diseases like cardiovascular disease.

Furthermore, there are many cell types that remain to be assessed, like neurons and other brain cells. We’ve barely seen the tip of the iceberg with respect to how different past metabolic and environmental exposure impact gene expression across the body.

(3) Knowledge is Power!

Understanding these mechanisms is the first step to developing therapies/protocols to changes our epigenome and engineer our advantage over what nature seems to have planned. Or, put another way, learning about mechanisms teaches us how to best take advantage of our evolutionary priming to work with, rather than against, nature’s sometimes confusing design.

Full Video, now available on YouTube as well.