Metabolic Adaptions to Weight Loss


What makes it hard to keep weight off? We need to understanding the elements working against us. 

Take away the burden of guilt, “it’s all my fault I regained my weight.”

It is NOT that person, it is NOT a lack “will power.”

The evidence showing it’s not “just you:”

NHANES 1999‐2006, n=14,306. (study not in a controlled environment)

Stats showing how successful weight loss maintenance is
People who lost “x%” of weight and kept it off at one year:

  • 5% WL(weight loss): 33% of people can maintain that weight loss at one year
  • 10% WL: 17% maintained at one year
  • 15% WL: 8.5% maintained it
  • 20% WL: now just 4.4% of people can maintain it at one year.
  • (Kraschnewski et al. Int J Obes 2010:34:1644)

“Weight loss Maintenance Randomized Controlled Trial (ie done in a controlled environment)

Group based behavioral intervention 
Followed DASH diet over 6 months
180 min physical activity a day

  • If they lost weight they were randomized into 3 groups: 
    • Self directed (n-341), 
    • Interactive technology(347)(IT)- participants were encouraged to regularly log on to an interactive Web site 
    • Personal Contact (n=341)(PC):monthly individual contact with an interventionist
    • All groups encouraged to get physical activity to at least 225 minutes per week
    • Both PC and IT –based interventions reinforced the key theoretical constructs (motivation, support, problem solving, and relapse prevention) that had been incorporated in phase 1. In addition, both active interventions incorporated features found to be associated with maintenance of behavior change in previous studies, such as continual intervention contacts, self-monitoring, accountability, prolonged continuous contact, and motivational interviewing.
  • all groups began to gain weight, not back to baseline, but regained. (graph pictured).
  • Svetkey LP, et al. JAMA 2008;299:1139‐1148

So why do so many people have trouble maintaining even just a 5% weight loss, and why does this number worsen with the more weight that has been lost??? 

    • One would think the more weight you lose the better chance you would have at maintaining it, after all you spent more time getting 35% body weight off compared to 5%.
    • what changes as we lose more and more weight?
    • what is the biology driving us to regain. 

Two areas that is monitoring our energy stasis/energy balance
1: The GI tract 
 Influencing satiety signals- in particular Ghrelin, GLP1 and PYY have duel functions

      • gastric motility, insulin sections, but also informs the brain of when to eat and when not to eat.
      • How do they stimulate the brain from the gut? Transmit signal either via the vagus nerve or release into the blood and go up to the brain 
      • Ghrelin: tells us we are hungry

Centers are very high up in the gastrointestinal tract
“I’m hungry but not starving anymore” = ghrelin levels are coming down

      • CCK, GLP1 PYY centers found in the small intestine

Woods, S. C. et al. J Clin Endocrinol Metab 2008;93:s37-s50

Timeline of hunger

Morning you feel hungry = ghrelin starts to climb
After breakfast - less hungry = ghrelin is declining and you have gastric distention
Before lunch ghrelin again climbing, gastric distention reduced = hunger increasing
After lunch ghrelin declines again
And so on and so on.

Sumithran et al. N Engl J Med 2011;365:1597-1604
N = 50 ppl
8 week diet, Very low cal diet (“VLCD”)
They had 14% weight loss, followed after weight loss for a year.
After weight loss they ate 550Cal breakfast and measure ghrelin response and PYY
---> ghrelin had the same slope down and then back up during and following a meal, BUT their levels were higher compared to their levels when they were 14% lighter. 

      • So the same person with the same meal after a weight loss has higher levels of ghrelin circulating 

(Take away after a weight loss people experience more hunger than ever)

--->PYY: as they lose weight it starts to drop---> clinical presentation = more desire to eat

(take away the desire to eat goes up, and the hunger as one loses weight

Fat Cells - Leptin

Fat cells: Help to initiates hunger, and can stop hunger (eg what initiates satiety)

This system more monitors long term overall status of the body (vs day to day as above)


      • Produced by fat cells - the more fat cells you have the more leptin you have
      • Tells the brain when you lost weight (for the most part)
        • As you lose weight (lose leptin making fat cell) the brain senses the decrease ---->----> decrease in sympathetic tone 

(decrease in “metabolism” to help bring leptin (and fat cells) back to its homeostasis (ie regain weight)

Study: Wadden TA et al. J Clin Endocrinol Metab 1998;83:214-218:
Looked a two diets that led to weight loss 

      • 1200 Cals/d weeks 2-20; then 1200-1800 weeks 21-40
      • 1000Cal/day week 2-13, then 1200Cal week 14-20, then 1200-1800 Cal weeks 21-40


At the end of the 40 week both groups lost about 12%

Changes in leptin seen:

      • plummets very quick, out of proportion to amount of fat lost; in other words as body fat decreases leptin goes down quicker
      • even after 40 weeks(just over 3 months) the leptin level don’t go back to where it was

 (so the brain doesn’t care if you are obese, the brain just doesn't like the change)



  • Body weight is regulated by hunger and satiety signals from the GI tract and Fatty tissues
  • Neurohormonal systems that can sense a reduction in body weight lead to adaptive sympathetic tone changes trying to “correct” the weight loss

My point I would want everyone to take away: 

    • Anticipate losing weight to be a progressively difficult thing: especially in terms of having to “feel” the sensation of hunger.
    • Working on behavioral changes in imperative: monitoring, logging, etc.
    • Find a long term support system, accountability always will be important. Even better is a support system that is fun, it makes you want to “be better.”
    • Lastly it crazy bugs me when anyone in the weight loss world tells their patients or clients “I’ll teach you everything you need to know for you to lose weight and keep it off.” Yet I never hear them tell you it’s going to actually get harder and harder (especially to those with more that 20lbs to lose. Coming from a person who bounced around from program to program spending all kinds of money….in the future if you hear these types of words, I would stay away from them. 
    • In the end, weight loss is about 40% knowing what to do and 60% dealing with hunger. #cleanoutyourpantry 😉