Why is it so Hard to Maintain a Reduced Body Weight?

[Guest guest]

Article sent to me this am - source and author unknown. Interesting

Sandy

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Why is it so Hard to Maintain a Reduced Body Weight?

Posted: 18 May 2011 06:00 AM PDT

Yesterday, I had the pleasure of attending a lecture by Rudy Leibel from

Columbia University, who is perhaps best known for his considerable

contributions to our current understanding of energy metabolism.

The talk was hosted by Colmers as part of the University of Alberta

Merck Translational Lecture Series.

In his presentation, Leibel addressed the issue of why it is so hard to keep

weight off - in fact, even in people who undergo bariatric surgery, weight

always comes back when surgery is reversed.

One of the key underlying problems is that when people lose weight, their energy

expenditure does not simply fall to that of the energy expenditure of a person

`naturally' at that lower weight - it drops to levels far greater than expected.

Thus, a formerly-obese person burns 20% less calories than a never-obese person

of that lower weight - or in other words a 200 lb person, who loses 40 lbs burns

about 20% fewer calories than someone who is 160 lbs, but has never been obese.

On top of this, the formerly-obese person experiences hunger, cold intolerance,

and other behavioural and metabolic changes that make sustaining this lower body

weight difficult.

From an evolutionary sense, this makes a lot of sense, as maintaining or

`defending' fat stores in the past has always been vital for human survival and

therefore complex biological systems have evolved to readily take up and store

excess calories when available and reduce caloric expenditure when times are

tough.

In a large series of carefully conducted energy balance studies in humans,

Leibel examined the impact of weight loss on energy expenditure, energy intake,

neuroendocrine function, autonomic physiology, metabolism and brain imaging.

Whereas a short-term increase in body weight by 10 % results in a transient

increase in energy expenditure, this returns to baseline, when the weight is

lost. This means that weight-loss per se does not reduce energy expenditure.

On the other hand, a 10% drop in body weight immediately reduces energy

expenditure by as much as 20%.

Interestingly, this fall in energy expenditure is not simply due to a fall in

metabolic rate, but largely due to a decline in activity expenditure. This means

that the body 'saves' energy not simply by turning down the furnace, but by

becoming substantially more `fuel efficient' during activity. In other words,

someone who loses weight, will burn substantially fewer calories for a given

amount of exercise than for the same amount of exercise performed before weight

loss.

Much of this increase in `muscle efficiency' can be attributed to the remarkable

fall in the fat tissue-derived hormone leptin that occurs with weight loss.

Obese individuals apparently need a higher level of leptin to sustain energy

balance. When they lose weight, thereby lowering their leptin levels, the system

will aim to increase body fat levels to once again produce enough leptin to

suppress the orexogenic response. Thus, weight reduction looks like `leptin

deficiency' to the brain, which it seeks to correct, by promoting weight gain.

The importance of leptin in this `defense' response is clearly evident from both

animal and human studies, in which leptin levels were maintained at or restored

to pre-weight loss levels despite weight loss, by injecting leptin at levels

just high enough to `mimic' baseline levels.

In all of these experiments, using exogenous leptin to restore leptin levels to

baseline, abolished the `defense' mechanisms including the decline in total

non-resting energy expenditure, thus making it easier to keep the weight off.

This `relative leptin-deficiency' dependent improvement in muscle efficiency

with weight loss can be clearly and consistently demostrated at the functional

(exercise), imaging (MRI) and biological (biopsy) level.

Apart from reversing the improvements in muscle efficiency, Leibel also showed

how the increased activation of hunger and appetite centres in the brain with

weight loss can be reversed by leptin replacement. Thus, administration of

leptin to individuals post-weight loss, reverses the decreased/delayed satiation

and decreased perception of caloric density that would act to restore body

weight to baseline.

Increases in the weight set-point occur with chronic weight gain, neuronal loss

of aging, puberty and pregnancy. Unfortunately, lowering this threshold is far

less likely, requiring such drastic measures as hypothalamic lesions or

cachexia.

Thus, from an energy regulatory perspective, weight loss induces a

`non-physiological' state that can be restored to a `physiological' state by

leptin administration at levels high enough to mimic baseline levels.

So why is leptin not being sold to maintain weight loss? Because there is

currently no regulatory pathway to license drugs that prevent weight regain.

Regulators like the FDA and the EMEA simply lack a sound understanding of the

complex physiology of weight regulation because after all, in weight management,

the problem is never how to lose weight - the problem is always how to keep it

off.

Unfortunately, based on the current guidelines for obesity drugs, there is no

way for a pharma company to even apply to have a drug licensed that does not

help reduce body weight (which leptin does not) but merely helps people keep

weight off (which leptin does).

This is a shame, because in the end replacing leptin may well be the safest way

to restore the `physiological' state of being obese by correcting the

`unphysiological' state of having lost weight, which essentially drives weight

regain.

AMS

Edmonton, Alberta

[Guest guest]

Thiscarticlecwas blogged by Dr Sharma, the main bariatric researcher an surgeon

in Canada. Below is his website. He sends out a daily newsletter of pertinent

bariatric info. A good newsletter to subscribe to.

http://www.drsharma.ca/

Sent from my iPad.

Barb