January 8, 2022

Weight Set Point Theory

The real challenge with weight loss is keeping the weight off. 

When you lose a significant amount of weight (greater than 10% is the number that’s typically used, though certainly there is individual variability), the body does what it can to return to its original weight, leading to the much-heralded phenomenon of yo-yo dieting.  The body seems to have a weight set point that it defends despite the extent of its internal stores of energy (in the form of fat).   The set point can increase over time because of environmental and physiological reasons.  For example the hormonal changes of pregnancy or significant prolonged cortisol release from stress.  Alternatively being placed in a new food environment such as going to college or working from home during a pandemic.  These changes can raise a person’s set point, but lowering it is a harder job.  Regardless of where the set point resides, when we lose weight below the set point, the body counters with metabolic adaptive physiological processes that evolved to defend itself from starvation. These include the following mechanisms.

  1. Thyroid function changes.  Reverse T3 increases, T3 and T4 decrease, effectively rendering you hypothyroid
  2. Muscle efficiency increases (improved muscle function per calorie, less wasted calories)
  3. Neuro-humoral changes:  leptin, CCK, peptide YY all DECREASE, thus removing inhibitory actions on ghrelin, increasing appetite
  4. Decrease in resting energy expenditure due to weight loss and less available metabolically active tissue
  5. Adaptive thermogenesis decreases resulting in reduced resting metabolic rate
  6. Decreased sympathetic tone, increased parasympathetic tone
  7. Commitment amnesia:  relapse of maintenance behavior that were required to lose the initial weight

As a result, fewer than one out of six people who have lost a significant amount of weight can keep it off after a year. Even more alarmingly, there is a concern that by weight cycling, you end up resetting your basal metabolic rate lower across all weights.  So even after you regain the weight, you are still burning less calories, even at rest.  Why might this happen?

With weight regain, the body’s imperative can be understood as follows:  it wants to reconstitute fat free mass (FFM).  This includes lean muscle but also the weight of organs, bones and other non-fatty tissues in the body.   In Keys’ famous Minnesota weight loss experiment with conscientious objectors to WW2, over-eating and weight gain did not abate until FFM was reconstituted.  During weight regain, there was a desynchronization in the reconstitution of fat mass and fat free mass, so subjects ended up with an overshoot of fat return.  Meaning when you regain the weight, you end up with an increased percentage of fat as compared to muscle.  Fat is a less metabolically active tissue and so you should theoretically have a lower BMR at the new weight, and this is what is observed.

Is there a solution?  Possibly, and we’ll get to that.

Where does the set point reside?

How is this set point encoded and where does it reside in the body?  We don’t really know for sure but allost certainly in the subcortical regions of the brain.  More specifically the hypothalamus.  Possibly more specifically, in the arcuate nucleus of the hypothalamus, where the major nuclei relevant to maintenance of weight reside.  One theory is that specific neuronal cells called astrocytes in the arcuate nucleus either sense changes in nutrition or somehow are attuned to loss of weight, possibly in relation to lepton levels.  As a result they are activated in a process known as reactive gliosis.[i]  Other epigenetic changes are encoded in various parts of the brain and body as a consequence of weight loss leading to the defended phenotype.  The symptoms of this condition are excess hunger and reduced satiety as compared to normal people.  Nobody knows exactly what the thermostat is measuring.  It could be circulating fat or lepton, it could be some factor related to fat free mass.

Bariatric surgery seems to evade some of the post-weight loss changes related to a set point, but why this happens is not completely understood.  The commonly performed surgeries change the composition and concentration of bile-acids, which are important signals of satiety.  Also, because of structural changes in the gut, more nutrition passes to the distal part of the intestine causing increases in anorexigenic hormones such as GLP1 and PYY (hindgut hypothesis).  There may also be changes in direct signaling to the CNS.  Then the mechanical issues: the stomach is smaller, there is a fear of dumping syndrome if you eat too fast, etc.  All of these factors contribute to a functional reduction in set point.  But bariatric surgery is not the only way to lower the set point.

But then how do we keep the weight off?

One basic principle is that if you must lose large amounts of weight, then do it slowly so that the body gradually adjusts to a lower set point.    Losing weight more deliberately and pausing between plateaus seems to help people evade the set point phenomenon and thus maintain reduced body weight,[ii] though to be clear, this finding is anecdotal and lacks experimental proof.

Beyond that, attention needs to be paid to muscle.  When you lose weight, you lose both fat and fat free mass.  Fat free mass includes the weight of organs and other tissues, but also muscle.  When you regain the weight in the context of increased muscle mass, you will regain fewer pounds of fat.  In other words, muscle mass will protect against fat regain.  There are medications that should be used to mitigate the set point or even reset it. Ultimately, weight loss needs to be done in a controlled fashion with a plan, with frequent pauses to permit the body to catch up.  Muscle mass facilitates this process.

Dietary characteristics are also important.  I suggest a diet that is somewhat less palatable, with less sugar, salt, fat and calorie density, more fiber.  The diet will be satiating but less rewarding.  If you can stick to a diet like this for a few weeks, it will change the way your brain defends its adiposity.

Finally no discussion of weight is complete without a mention of exercise, sleep and stress management.  While these may not be critical in weight loss, they are important in resetting the ponderostat, or body weight set point.

[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977167/pdf/main.pdf

[ii] https://www.nature.com/articles/ijo2017224

Also https://www.sciencedirect.com/science/article/abs/pii/S001650851730152X

Leave a Reply

Your email address will not be published. Required fields are marked *