Fasting appetite-related gut hormone responses after weight loss induced by calorie restriction, exercise, or both in people with overweight or obesity: a meta-analysis

Int J Obes (Lond). 2025 May;49(5):776-792. doi: 10.1038/s41366-025-01726-4. Epub 2025 Feb 10.

Abstract

Objectives: Altered appetite-related gut hormone concentrations may reflect a physiological adaptation facilitating weight regain after weight loss. This review investigates hormonal changes after weight loss achieved through calorie restriction (CR), exercise (EX), or both combined (CREX).

Methods: A systematic search of PubMed (MEDLINE), EMBASE, SPORTDiscus, Cochrane Library, Web of Science, and ClinicalTrials.gov was conducted to identify randomised controlled trials (RCTs) and non-RCTs reporting in a fasting state either pre- and post-intervention appetite-related hormone concentrations or the changes therein after weight loss. The hormones examined were ghrelin, peptide tyrosine tyrosine (PYY), glucagon-like peptide -1 (GLP-1), and cholecystokinin (CCK), in their total and/or active form. Standardised mean differences (SMD) were extracted as the effect size.

Results: 127 studies were identified: 19 RCTs, 108 non-RCTs, 1305 and 4725 participants, respectively. In response to weight loss induced by CR, EX or CREX, the meta-analysis revealed an increase in total ghrelin from both RCTs (SMD: 0.55, 95% CI: 0.07-1.04) and non-RCTs (SMD: 0.24, 95% CI: 0.14-0.35). A decrease in acylated ghrelin was identified for RCTs (SMD: -0.58, 95% CI: -1.09 to -0.06) but an increase was observed for non-RCTs (SMD: 0.15, 95% CI: 0.03 to 0.27). Findings also revealed a decrease in PYY (total PYY: SMD: -0.17, 95%CI: -0.28 to -0.06; PYY3-36: SMD: -0.17, 95%CI: -0.32 to -0.02) and active GLP-1 (SMD: -0.16, 95% CI: -0.28 to -0.05) from non-RCTs. Changes in hormones did not differ among the three interventions when controlling for weight loss. Meta-regression indicated that greater weight loss was associated with a greater increase in total ghrelin.

Conclusions: Weight loss induced by CR, EX, or CREX elicits an increase in total ghrelin, but varied responses in other appetite-related hormones. The extent of weight loss influences changes in appetite-related gut hormone concentrations.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Appetite* / physiology
  • Caloric Restriction*
  • Exercise* / physiology
  • Fasting* / physiology
  • Gastrointestinal Hormones* / metabolism
  • Ghrelin / metabolism
  • Humans
  • Obesity* / diet therapy
  • Obesity* / metabolism
  • Obesity* / physiopathology
  • Obesity* / therapy
  • Overweight* / metabolism
  • Overweight* / therapy
  • Peptide YY
  • Randomized Controlled Trials as Topic
  • Weight Loss* / physiology

Substances

  • Gastrointestinal Hormones
  • Ghrelin
  • Peptide YY