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Comment by smooth_remmy | Hacker News Reader

The point is that you could gain back the original weight plus more. Most adults who become obese have not increased their number of fat cells - their fat cells just become larger.

The GLP-1 drugs literally increase the number of fat cells.

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They've studied this, they put people om semaglutide then took them off of it for a year. Looks like every other weight loss intervention.

https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.147...

> The point is that you could gain back the original weight plus more.

This is also common in all weight loss interventions, though the reason is generally from metabolic slowdown, not the creation of new adipose tissues.

I suppose the concern goes something like this. Under certain metabolic conditions, each fat cell (in a region) decides it needs to be size X, and grows / shrinks accordingly. And under other conditions, each fat cell (in the same region) decides it needs to be size X*3.

If there are more fat cells, then and they all decide to increase in size, then that could be a substantial weight gain, beyond what would be expected otherwise.

How does liposuction fare in long term fat loss?

> Weight gain was reported in 43 percent of the responders, with 56 percent of them gaining between 5 and 10 pounds 6 months after their surgery. Fat return was reported in 65 percent of the responders. https://pubmed.ncbi.nlm.nih.gov/16651945/

Liposuction isn't a solution for fat loss beyond some localised cosmetic reduction. You can't use it to put a morbidly obese person in normal BMI range.

My point is that you end up with fewer fat cells, but unsure whether this has any impact on weight regain.

(Which is worth assessing if there are concerns about these drugs increasing the number of fat cells (otherwise unusual in adulthood) and creating a risk of fat volume rebound beyond initial levels after discontinuation).

Weight is back to baseline within a few months after lipectomy and sometimes greater than baseline. In animal models there is regeneration of fat cell number following lipectomy along with increase in cell size, and which mechanism predominates depends on how large the fat cells were before (manipulated by reducing food). This is the critical fat cell size hypothesis, and in humans there is similarly evidence that fat cell number increases (hyperplasia) in advanced stages of obesity after the cells reach critical size (hypertrophy) but I'm not aware of that being studied in situ in lipectomy recovery. I'd make a confident guess that it depends on how obese the patient is and perhaps their baseline number of fat cells.

But there are a lot of different mechanisms and feedbacks at play and I'm not sure how much insight can be gained from comparing localised lipectomy to systemic adipocyte proliferation resulting from a drug.

This sounds especially bad cosmetically, because the fat will show up in some place it didn't used to. I would imagine it could make you look even worse.

Liposuction is no answer. Your body puts back the removed fat cells in other places.

The human body has VERY strong setpoints about weight. Fat cells "remember" the weight that you had when they were created. You have to hold your weight at a point for something like 3-5 years before your body relents enough that the setpoint moves.

How do fat cells encode the information about one's weight when the cells are created?

It's probably not the fat cells, it's much more likely the hypothalamus.

Maintenance of lipid concentration when formed.

The aggregation of the tiny setpoints creates your larger setpoint by either drawing out from or pushing into your bloodstream the lipids that they have.

This is one of the most infuriating things about the "you just need to eat less" crowd. That's simply the first step. But you somehow need to maintain that for years while your body readjusts since fat cells turn over fairly slowly in your body (about 20-25% per year).

Maintaining a lower body weight while your body is actively fighting you for years is a superhuman level of willpower that very few of us can muster.

Damn, I wish I'd known this decades ago

I specifically asked doctors and they were like "I dunno. Well, that was a fun 5 minute conversation, give me $300"

I guess it's never too late, though. I've been slacking off on getting in shape, since it does take raw willpower 20 times a day every day in order to get there and stay there, and it's not that compelling to think that I'm going to be stuck rolling willpower checks all the time forever.

If I just have to get in shape and force myself to stay that way through raw willpower for ~4 years in order to stay that way for free afterward, though, that sounds like a more worthwhile goal

It is never too late. And please don't beat yourself up when you fail. Simply sigh, dust yourself off, and try to do better. Given that you have to maintain this for years, you will sometimes fail--it's inevitable.

There is increasing amounts of science behind this stuff, but it's also buried behind a gargantuan pile of crap.

Good luck.

> You have to hold your weight at a point for something like 3-5 years before your body relents enough that the setpoint moves.

Is there any evidence of this? I've never seen any evidence the setpoint ever moves down.

It's what I thought of here also. Most notably, liposuction has faired very poorly in studies of long-term health outcomes. Without the requisite changes in lifestyle or metabolism the fat that gets sucked out is replaced very quickly and has almost no decrease in risk of obesity-related illnesses.

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