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Physiological responses to weight loss trigger weight regain1-5

Mary, with BMI of 44, is struggling with weight regain

The role of the gut-brain axis in appetite control6-8

  • Communication between the gastrointestinal tract and the central nervous system are key components in appetite regulation 
  • The gut-brain axis, containing both neural and humoral components, has particular significance in food consumption control 

Metabolic responses to weight loss defend baseline body weight9,10

  • After weight loss, metabolic adaptation leads to decreases in resting metabolic rate and increases in energy intake 
  • Weight loss can reduce resting metabolic rate by ~15%, which consequently decreases total energy expenditure
  • Maintained reduction in body weight of 10% or more is met with a disproportionate response in energy expenditure and increased muscle efficiency

Weight loss in people with obesity causes changes in appetite hormones that increase hunger and the desire to eat for at least 1 year1

  • Multiple hormones, such as ghrelin, GLP-1, and leptin, play an important role in appetite regulation.6

Metabolic adaptions to weight loss include1-5

Role of hormones in regulating appetite

In a 62-week study of 50 patients with a BMI ranging between 27 kg/m2to 40 kg/m2:

  • The hunger hormone Grehlin remained elevated for at least 1 year following weight loss1
  • Satiety hormones Peptide YY, Amylin, and CCK remained reduced for at least 1 year following weight loss1


Also in The Science of Obesity:



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  1. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604.
  2. Schwartz A, Doucet É. Relative changes in resting energy expenditure during weight loss: a systematic review. Obes Rev. 2010;11(7):531-547.
  3. Sumithran P, Proietto J. The defence of body weight: a physiological basis for weight regain after weight loss. Clin Sci (Lond). 2013;124(4):231-241.
  4. Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes (Lond). 2010;34(suppl 1):47-55.
  5. Rosenbaum M, Kissileff HR, Mayer LE, Hirsch J, Leibel RL. Energy intake in weight-reduced humans. Brain Res. 2010;1350:95-102.
  6. Valassi E, Scacchi M, Cavagnini F. Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis.2008;18:158‒168. 
  7. Woods SC, Seeley RJ.Understanding the physiology of obesity: review of recent developments in obesity research.Int J Obes Relat Metab Disord. 2002;26(Suppl 4):S8-S10.
  8. Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science. 2005;307(5717):1909-1914.
  9. Lam YY, Ravussin E. Analysis of energy metabolism in humans: a review of methodologies. Mol Metab. 2016;5(11):1057-1071.
  10. Goldsmith R, Joanisse D, Gallagher D, et al. Effects of experimental weigh perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects. [published online 2009 Nov 4]. Am J Physiol Regul Integr Comp Physiol. 2010;298(1):R79-R88.