Your Fat Cells Remember! Can You Heal the Metabolic Scar of Obesity?

new research in a top science journal has revealed how fat cells retain a memory of obesity after weight loss and how this could impact your ability to maintain a healthy body composition I want to show you what they found in this new paper reveal what appears to be a pessimistic story but ultimately leave you with some important takeaways that I hope you'll find empowering or at least useful now the paper in question was just published in nature and is entitled tissue retains an epigenetic memory of obesity after weight loss atopos tissue refers to body fat

in epigenetic memory well if you don't know what that is I'll explain that momentarily with an analogy but first let me provide you with a framework a background for this paper you're probably aware of the yo-yo diet effect whereby people who lose excess body fat are prone to gain it back think about the Biggest Loser where people lose a ton of weight quickly but typically if you follow them up you'll find that their metabolism is slow and they end up gaining most if not all of the weight back which is a real bummer but is

this weight regain phenomenon a purely behavioral phenomenon or are there deeper metabolic mechanisms at play this new research argues the latter 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 after bariatric surgery and they measured gene expression profiles from their fat cells the controls and also those with obesity at the time of surgery and 2 years later after substantial weight loss at least a quarter of their body weight and they found significant changes in fat cell ocy as

well as fat cell precursor and also other cell type gene expression patterns overall what the researchers found is that fat cells from individuals with a history of obesity even after weight loss showed down regulation so less gene expression related to metabolic functions in upregulation more gene expression of genes related to inflamatory functions and inflammation thus in the author's own words they conclude that these results indicate that obesity induces cellular and transcriptional obesogenic changes in fat cells which are not resolved following significant weight loss the fat cells retain a memory of having been fat fat cells

from people who had previously had obesity were less metabolically healthy and generally more inflammatory that was the big picture finding now before I get into some more of the results I wanted to do a quick nerd aside nerd alert a quick tangent you can skip forward in the video a little bit if you don't want the details but I actually did want to dig into the technique they Ed to measure gene expression profiles in case you're interested so what they did it's called single nucleus RNA sequencing where the nucleus is kind of the conductor of

the cell and what they do is they take cells and they break them up and they separate out the nuclei via centrifugation and then you can actually sort types of cells or cell nuclei with something called fluorescence activated cell sorting or facts where fluorescently labeled antibodies are used to tag different nuclei from different cell types and that permits them to be identified and sorted with a literal laser based on their fluorescent properties which is freaking cool it's actually really cool that this even works anyway that was the nerdy aside back to what matters for you

to get more granular in this study the researchers did then experiments on mice where they fattened some mice with a high sugar high fat obesogenic diet and then normalized the weight of those mice through dietary restriction on a normal Chow diet and compared the mice who had obesity but recovered to those mice who never had obesity in the first place and they found consistent with the human data we already reviewed that there was persistent expression patterns whereby genes that were downregulated during obesity with the respective metabolic pathways remain downregulated things like fatty acid oxidation and

mitochondrial signaling and obesity also left in epigenetic memory in terms of increasing inflammatory pathway so just like in the humans metabolic pathways tend to be downregulated inflammatory Pathways tend to be upregulated but now I want to get to how does all of this work and I want to use an analogy the analogy is this your genetic code your DNA is kind of like a book and even though all the cells in your body contain your full genetic code they are different your eye cell is different than a bone cell is different than a skin cell

why because different cells read different pages in the book some pages are open some pages are shut depending on the cell type what's more cells can bookmark or dogear various Pages for easy access as they read through the book in the cell this is kind of like an epigenetic change where tags are put on DNA or the protein complexes around which DNA is wound and this makes it easier or harder to gain access to certain pages in your genetic code which changes the gene expression profiles in those cells hopefully that makes sense and that's how

cells develop a memory of past events including the memory in fat cells of oh I was once an obese fat cell if it's not too dark to say and to mix in another analogy it's kind of like PTSD for fat cells now another really important question are these changes functionally or clinically meaningful and it would appear so human observational and clinical data suggest that those who have lost weight are more prone to put that weight back on and although of course in Free Living humans it's really 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 you can do parallel carefully controlled Mouse experiments which they did in this study and which should generalize to humans given that these pathways are pretty conserved and this all does indeed strongly suggest that a history of obesity does predispose fat cells to take up more sugar readily this was shown in the paper build up fat stores more in response to insulin and also things like develop fatty liver more easily the history of obesity does leave a memory a metabolic fingerprint

on the body now those are the main findings of the paper and it's a bit of a dark story I'll admit because it suggests that having had obesity is kind of like a screw you from biology no fair right well I have a different take and a few concluding thoughts that I want to share with you first it's true that a history of obesity even if one is now lean may put a person behind the metabolic eightball however this might not be permanent because bear in mind those who had obesity in this study and then

recovered from obesity had a relatively short time frame of being newly not obese as compared to the time course over which they initially developed the Obesity which presumably took decades so what we don't know but what I suspect is that if someone is able to maintain a lean healthy weight for a long enough time the epigenetic memory may fade thus it's possible although not proven that the longer you can maintain a healthy lean weight the easier it becomes and I think that's an uniting thought also I'd maintain that your present lifestyle choices today and tomorrow

and going on to the Future still have the dominant effect even if your metabolic Road might be rockier it doesn't mean you shouldn't or can't Traverse it these data do not say that one can't maintain a lean healthy weight after having had obesity they just kind of acknowledge that biology can be a jerk sometimes and it can biology isn't always Fair all right two the epigenetic memory is not specific to fat cells there were also changes for example in endothelial cells that line your blood vessels thus a history of obesity could predispose individuals to diseases

like cardiovascular disease furthermore and as pointed out by the authors 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 exposures can impact gene expression across the body over time and then three knowledge is power it truly is understanding these mechanisms is the first step to developing therapies and or protocols to change our epig genome and engineer our advantage over what nature seems to have planned for us or to put it another way

learning about these metabolic mechanisms teaches us how to best take advantage of our evolutionary priming to work with rather than against Nature's sometimes confusing design now I want to ask you how do you feel about these data do they bring you down or do they Empower you do they take the wind out of your sails or do they motivate you because you better understand what's going on in your body I think any of these reactions is fair but I also know for a fact that if you're watching this video up until this point it means

that you're metabolically curious and in the Arsenal of tools that you have to achieve excellent metabolic Health metabolic Curiosity has to be be at the top of the list so good on you and stay curious I hope you found this interesting [Music]