International Journal of Obesity (2014) 38, 388–396; doi:10.1038/ijo.2013.118; published online 23 July 2013

Adaptations of leptin, ghrelin or insulin during weight loss as predictors of weight regain: a review of current literature

K Strohacker1, J M McCaffery1, P S MacLean2 and R R Wing1

  1. 1Department of Psychiatry and Human Behavior, The Miriam Hospital and Warren Alpert School of Medicine at Brown University, Providence, RI, USA
  2. 2Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, Center for Human Nutrition, University of Colorado Anschutz Medical Campus, Denver, CO, USA

Correspondence: Dr RR Wing, Weight Control and Diabetes Research Center, The Miriam Hospital, 196 Richmond Street, Providence, RI 02904, USA. E-mail:

Received 11 March 2013; Revised 21 May 2013; Accepted 14 June 2013
Accepted article preview online 26 June 2013; Advance online publication 23 July 2013



Numerous laboratory studies involving both animal and human models indicate that weight loss induces changes in leptin, ghrelin and insulin sensitivity, which work to promote weight regain. It is unclear, however, whether these biological changes serve as a biomarker for predicting weight regain in free-living humans in which biological, behavioral and environmental factors are likely at play. We identified 12 studies published between January 1995 and December 2011 that reported changes in leptin, ghrelin or insulin during intentional weight loss with a follow-up period to assess regain. Two of the nine studies examining leptin suggested that larger decreases were associated with greater regain, three studies found the opposite (smaller decreases were associated with greater regain), whereas four studies found no significant relationship; none of the studies supported the hypothesis that increases in ghrelin during weight loss were associated with regain. One study suggested that improvements in insulin resistance were associated with weight gain, but five subsequent studies reported no association. Changes in leptin, ghrelin or insulin sensitivity, taken alone, are not sufficient to predict weight regain following weight loss in free-living humans. In future studies, it is important to include a combination of physiological, behavioral and environmental variables in order to identify subgroups at greatest risk of weight regain.


weight loss; weight regain; appetite hormones; review; free-living humans

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