Long-Term Persistence of Hormonal Adaptations to Weight Loss

TLDR

Weight loss induces changes in peripheral hormones that regulate body weight, and long‑term strategies may be required to counteract these adaptations. The study aimed to determine whether hormone changes after weight loss are transient or persist, by enrolling 50 overweight or obese patients in a 10‑week very‑low‑energy diet program. Researchers measured leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon‑like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, insulin, and subjective appetite at baseline, after 10 weeks, and at 62 weeks. Weight loss produced significant reductions in leptin, peptide YY, cholecystokinin, insulin, and amylin, increases in ghrelin, gastric inhibitory polypeptide, and pancreatic polypeptide, and heightened appetite, and these altered hormone levels persisted one year after weight loss. The study was funded by the National Health and Medical Research Council and others and registered at ClinicalTrials.gov (NCT00870259).

Abstract

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.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.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).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.).