Long-Term Persistence of Hormonal Adaptations to Weight Loss

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The below may be of interest:

http://www.nytimes.com/2011/10/27/health/biological-changes-thwart-weight-loss-e\

fforts-study-finds.html?_r=1 & smid=fb-share

For years, studies of obesity have found that soon after fat people lost weight,

their metabolism slowed and they experienced hormonal changes that increased

their appetites. Scientists hypothesized that these biological changes could

explain why most obese dieters quickly gained back much of what they had so

painfully lost.

But now a group of Australian researchers have taken those investigations a step

further to see if the changes persist over a longer time frame. They recruited

healthy people who were either overweight or obese and put them on a highly

restricted diet that led them to lose at least 10 percent of their body weight.

They then kept them on a diet to maintain that weight loss. A year later, the

researchers found that the participants' metabolism and hormone levels had not

returned to the levels before the study started.

The study, being published Thursday in The New England Journal of Medicine, is

small and far from perfect, but confirms their convictions about why it is so

hard to lose weight and keep it off, say obesity researchers who were not

involved the study.

They cautioned that the study had only 50 subjects, and 16 of them quit or did

not lose the required 10 percent of body weight. And while the hormones studied

have a logical connection with weight gain, the researchers did not show that

the hormones were causing the subjects to gain back their weight.

Nonetheless, said Dr. Rudolph Leibel, an obesity researcher at Columbia, while

it is no surprise that hormone levels changed shortly after the participants

lost weight, " what is impressive is that these changes don't go away. "

Dr. Bloom, an obesity researcher at Hammersmith Hospital in London, said

the study needed to be repeated under more rigorous conditions, but added, " It

is showing something I believe in deeply — it is very hard to lose weight. " And

the reason, he said, is that " your hormones work against you. "

In the study, ph Proietto and his colleagues at the University of Melbourne

recruited people who weighed an average of 209 pounds. At the start of the

study, his team measured the participants' hormone levels and assessed their

hunger and appetites after they ate a boiled egg, toast, margarine, orange juice

and crackers for breakfast. The dieters then spent 10 weeks on a very low

calorie regimen of 500 to 550 calories a day intended to makes them lose 10

percent of their body weight. In fact, their weight loss averaged 14 percent, or

29 pounds. As expected, their hormone levels changed in a way that increased

their appetites, and indeed they were hungrier than when they started the study.

They were then given diets intended to maintain their weight loss. A year after

the subjects had lost the weight, the researchers repeated their measurements.

The subjects were gaining the weight back despite the maintenance diet — on

average, gaining back half of what they had lost — and the hormone levels

offered a possible explanation.

One hormone, leptin, which tells the brain how much body fat is present, fell by

two-thirds immediately after the subjects lost weight. When leptin falls,

appetite increases and metabolism slows. A year after the weight loss diet,

leptin levels were still one-third lower than they were at the start of the

study, and leptin levels increased as subjects regained their weight.

Other hormones that stimulate hunger, in particular ghrelin, whose levels

increased, and peptide YY, whose levels decreased, were also changed a year

later in a way that made the subjects' appetites stronger than at the start of

the study.

The results show, once again, Dr. Leibel said, that losing weight " is not a

neutral event, " and that it is no accident that more than 90 percent of people

who lose a lot of weight gain it back. " You are putting your body into a

circumstance it will resist, " he said. " You are, in a sense, more metabolically

normal when you are at a higher body weight. "

A solution might be to restore hormones to normal levels by giving drugs after

dieters lose weight. But it is also possible, said Dr. Jules Hirsch of

Rockefeller University, that researchers just do not know enough about obesity

to prescribe solutions.

One thing is clear, he said: " A vast effort to persuade the public to change its

habits just hasn't prevented or cured obesity. "

" We need more knowledge, " Dr. Hirsch said. " Condemning the public for their

uncontrollable hedonism and the food industry for its inequities just doesn't

seem to be turning the tide. "

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Long-Term Persistence of Hormonal Adaptations to Weight Loss

Priya Sumithran, M.B., B.S., Luke A. Prendergast, Ph.D., Delbridge,

Ph.D., Katrina Purcell, B.Sc., Arthur Shulkes, Sc.D., Adamandia Kriketos, Ph.D.,

and ph Proietto, M.B., B.S., Ph.D.

N Engl J Med 2011; 365:1597-1604October 27, 2011

Background

After weight loss, changes in the circulating levels of several peripheral

hormones involved in the homeostatic regulation of body weight occur. Whether

these changes are transient or persist over time may be important for an

understanding of the reasons behind the high rate of weight regain after

diet-induced weight loss.

Methods

We enrolled 50 overweight or obese patients without diabetes in a 10-week

weight-loss program for which a very-low-energy diet was prescribed. At baseline

(before weight loss), at 10 weeks (after program completion), and at 62 weeks,

we examined circulating levels of leptin, ghrelin, peptide YY, gastric

inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide,

cholecystokinin, and insulin and subjective ratings of appetite.

Results

Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of

leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and

amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric

inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There

was also a significant increase in subjective appetite (P<0.001). One year after

the initial weight loss, there were still significant differences from baseline

in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin

(P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide

(P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001).

Conclusions

One year after initial weight reduction, levels of the circulating mediators of

appetite that encourage weight regain after diet-induced weight loss do not

revert to the levels recorded before weight loss. Long-term strategies to

counteract this change may be needed to prevent obesity relapse. (Funded by the

National Health and Medical Research Council and others; ClinicalTrials.gov

number, NCT00870259.)

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Carruthers

Wakefield, UK