Long-Term Persistence of Hormonal Adaptations to Weight Loss

Abstract

Most obese people can achieve short-term weight loss through dietary restriction, but only a small minority can maintain the reduced weight loss in the long-term. Failure to maintain the initial weight loss may be associated with acute compensatory changes in the circulating levels of several peripheral appetite-regulating hormones that occur as a physiologic response to caloric restriction. It is not known whether these changes are transient or are sustained over time. The present study investigated changes in blood levels of these hormones during 12 months in 50 overweight or obese patients without diabetes who had been on a very low energy diet in a 10-week weight-loss program. At baseline (week 0), week 10, and week 62, circulating levels of hormonal regulators of appetite and subjective ratings of appetite were examined. The hormones investigated included leptin, ghrelin, peptide YY, amylin, cholecystokinin, gastric inhibitory polypeptide, glucagon-like peptide 1, pancreatic polypeptide, and insulin. Weight loss at 10 weeks (mean [± SE], 13.5 ± 0.5 kg) was associated with significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P < 0.001 for all), and amylin (P = 0.002) and increased levels of ghrelin (P < 0.001), gastric inhibitory polypeptide (P = 0.004), and pancreatic polypeptide (P = 0.008). A significant increase occurred in subjective measures of appetite, including hunger and the desire to eat (P < 0.001). At 62 weeks, circulating levels of these hormones did not revert to baseline levels recorded before weight loss. Significant differences from baseline persisted in 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 subjective measures of appetite (P < 0.001). These findings indicate that the high rate of relapse in obese people after initial weight loss through dieting has a strong physiological basis. Successful long-term management of obesity will require the development of treatment strategies to counteract the persisting compensatory changes in circulatory levels of appetite-regulating hormones that encourage weight regain.