High fat diet causes rebound weight gain

David E. G. McNay, John R. Speakman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
4 Downloads (Pure)


Obesity is at epidemic proportions but treatment options remain limited. Treatment of obesity by calorie restriction (CR) despite having initial success often fails due to rebound weight gain. One possibility is that this reflects an increased body weight (BW) set-point. Indeed, high fat diets (HFD) reduce adult neurogenesis altering hypothalamic neuroarchitecture. However, it is uncertain if these changes are associated with weight rebound or if long-term weight management is associated with reversing this.

Here we show that obese mice have an increased BW set-point and lowering this set-point is associated with rescuing hypothalamic remodelling. Treating obesity by CR using HFD causes weight loss, but not rescued remodelling resulting in rebound weight gain. However, treating obesity by CR using non-HFD causes weight loss, rescued remodelling and attenuates rebound weight gain. We propose that these phenomena may explain why successful short-term weight loss improves obesity in some people but not in others.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalMolecular Metabolism
Issue number2
Early online date2 Nov 2012
Publication statusPublished - Apr 2013


  • Calorie restriction
  • Hypothalamus
  • Neurogenesis
  • Obesity
  • Rebound weight gain


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