Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations

Am J Clin Nutr. 2008 May;87(5):1238-46. doi: 10.1093/ajcn/87.5.1238.


Background: Weight regain after weight loss may not be due primarily to voluntary return to social habits but may be explained by changes in peripheral hormonal signals activating hunger and encouraging feeding behavior.

Objective: The objective of this study was to investigate physiologic adaptations to weight loss that may encourage weight regain.

Design: The study had a within-subject repeated-measure design [12 healthy, obese men, 33-64 y, body mass index (in kg/m(2)) 30-46] and was a clinical intervention investigation of circulating metabolites and hunger-satiety responses before and after weight loss. Measures included anthropometry (bioelectrical impedance, body weight, and waist circumference), concentrations of circulating hormones and metabolites [ketone bodies, free fatty acids (FFAs), insulin, leptin, glucose, and cholecystokinin (CCK)], and measures of hunger and satiety at baseline, 8 wk after weight loss with a very-low-energy diet, and 1 wk after weight maintenance.

Results: Weight loss led to a reduction in postprandial CCK secretion (P = 0.016). However, when subjects were ketotic (elevated circulating beta-hydroxybutyrate concentrations), CCK secretion was sustained at concentrations before weight loss. After weight loss, there were reduced postprandial FFA concentrations (P = 0.0005). The presence of ketosis sustained FFA to concentrations before weight loss (P = 0.60).

Conclusion: Rapid weight loss of approximately 10% of initial body weight results in a reduction in postprandial CCK and FFA concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adult
  • Anthropometry
  • Body Mass Index
  • Cholecystokinin / blood*
  • Cholecystokinin / metabolism
  • Eating / physiology*
  • Fatty Acids, Nonesterified / blood*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / physiology
  • Humans
  • Hunger / physiology
  • Insulin / blood
  • Ketone Bodies / blood*
  • Ketosis / blood*
  • Leptin / blood
  • Male
  • Middle Aged
  • Nutritional Physiological Phenomena
  • Obesity / blood
  • Obesity / diet therapy
  • Peptide Hormones / metabolism
  • Postprandial Period
  • Satiation / physiology
  • Signal Transduction
  • Weight Loss / physiology*


  • Fatty Acids, Nonesterified
  • Insulin
  • Ketone Bodies
  • Leptin
  • Peptide Hormones
  • Cholecystokinin