Long-term persistence of hormonal adaptations to weight loss.
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.).
Department of Medicine (Austin and Northern Health), University of Melbourne, Melbourne, VIC, Australia.
Priya
P
Sumithran
Luke A
LA
Prendergast
Elizabeth
E
Delbridge
Katrina
K
Purcell
Arthur
A
Shulkes
Adamandia
A
Kriketos
Joseph
J
Proietto
D015992:Body Mass Index; D001835:Body Weight; D002766:Cholecystokinin / Q000097:blood; D004038:Diet, Reducing; D005260:Female; D005768:Gastrointestinal Hormones / Q000097:blood*; D054439:Ghrelin / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D057194:Intention to Treat Analysis; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000178:diet therapy / Q000503:physiopathology; D019894:Peptide YY / Q000097:blood; D010455:Peptides / Q000097:blood; D017698:Postmenopause; D015431:Weight Loss / Q000502:physiology*
D005768:Gastrointestinal Hormones; D054439:Ghrelin; D020738:Leptin; D010455:Peptides; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin