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Do we really know what drives relapse in obesity management?

  • Catia Martins
    Correspondence
    Correspondence to: Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Affiliations
    Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olavs University Hospital, Trondheim, Norway
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      I have read with much interest the narrative review by Busetto and colleagues entitled “Mechanisms of weight regain”, recently published in your journal [
      • Busetto L.
      • Bettini S.
      • Makaronidis J.
      • Roberts C.A.
      • Halford J.C.G.
      • Batterham R.L.
      Mechanisms of weight regain.
      ]. There is no doubt that relapse in obesity treatment remains the main challenge in obesity management. Unfortunately, its etiology remains elusive and opposite to the authors` views there is no evidence supporting a role for compensatory biological mechanisms at the level of the homeostatic appetite control system or energy expenditure in this process. I invite the authors to read a review by my group on this topic entitled “Revisiting the Compensatory Theory as an explanatory model for relapse in obesity management” [
      • Martins C.
      • Dutton G.R.
      • Hunter G.R.
      • Gower B.A.
      Revisiting the compensatory theory as an explanatory model for relapse in obesity management.
      ], recently published in the American Journal of Clinical Nutrition.
      The authors state that “Altered gut hormone secretion profiles are a key part of this physiological drive to restore energy reserves and contribute to weight regain following dietary weight loss.” However, no references are given to support this statement. The authors later refer to the landmark paper by Sumithran et al. [
      • Sumithran P.
      • Prendergast L.A.
      • Delbridge E.
      • Purcell K.
      • Shulkes A.
      • Kriketos A.
      • et al.
      Long-term persistence of hormonal adaptations to weight loss.
      ], which shows that weight loss is associated with a sustained increase in the orexigenic drive to eat, as evidence for their statement. However, they forget to mention that Sumithran and colleagues [
      • Sumithran P.
      • Prendergast L.A.
      • Delbridge E.
      • Purcell K.
      • Shulkes A.
      • Kriketos A.
      • et al.
      Long-term persistence of hormonal adaptations to weight loss.
      ] found no association between the changes in appetite (either plasma concentration of appetite-related hormones or subjective feelings of appetite) following weight loss and relapse at 1-year follow-up (see supplementary material).
      Even though an increase in the secretion of the hunger hormone ghrelin, and subjective feelings of hunger, are a consistent finding following diet-induced weight loss (outside of ketosis) [
      • Sumithran P.
      • Prendergast L.A.
      • Delbridge E.
      • Purcell K.
      • Shulkes A.
      • Kriketos A.
      • et al.
      Long-term persistence of hormonal adaptations to weight loss.
      ,
      • Nymo S.
      • Coutinho S.R.
      • Eknes P.H.
      • Vestbostad I.
      • Rehfeld J.F.
      • Truby H.
      • et al.
      Investigation of the long-term sustainability of changes in appetite after weight loss.
      ,
      • Iepsen E.W.
      • Lundgren J.
      • Holst J.J.
      • Madsbad S.
      • Torekov SS.
      Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36.
      ], changes in the secretion of satiety peptides are conflicting [
      • Sumithran P.
      • Prendergast L.A.
      • Delbridge E.
      • Purcell K.
      • Shulkes A.
      • Kriketos A.
      • et al.
      Long-term persistence of hormonal adaptations to weight loss.
      ,
      • Nymo S.
      • Coutinho S.R.
      • Eknes P.H.
      • Vestbostad I.
      • Rehfeld J.F.
      • Truby H.
      • et al.
      Investigation of the long-term sustainability of changes in appetite after weight loss.
      ,
      • Iepsen E.W.
      • Lundgren J.
      • Holst J.J.
      • Madsbad S.
      • Torekov SS.
      Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36.
      ], likely due to different hormonal fractions being measured. Fig. 1 in Busetto and colleagues´ paper should reflect these inconsistencies. Not all studies show a reduction in the postprandial secretion of peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), in response to weight loss. For example, Iepsen et al [
      • Iepsen E.W.
      • Lundgren J.
      • Holst J.J.
      • Madsbad S.
      • Torekov SS.
      Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36.
      ], that the authors refer to, showed an increase in the postprandial release of total GLP-1 and PYY3-36 in response to diet-induced weight loss. Also, and opposite to what Busetto and colleagues state, weight loss maintenance in Iepsen´s study was not associated with higher circulating postprandial PYY3-36 and GLP-1 levels. In fact, Iepsen et al [
      • Iepsen E.W.
      • Lundgren J.
      • Holst J.J.
      • Madsbad S.
      • Torekov SS.
      Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36.
      ] did not perform any correlation analysis between changes in appetite following weight loss and weight loss maintenance at 1-year. Regarding the study by Thom et al. [
      • Thom G.
      • Dombrowski S.U.
      • Brosnahan N.
      • Algindan Y.Y.
      • Rosario Lopez-Gonzalez M.
      • Roditi G.
      • et al.
      The role of appetite-related hormones, adaptive thermogenesis, perceived hunger and stress in long-term weight-loss maintenance: a mixed-methods study.
      ], I suggest the authors read my letter to the editor [
      Martins C. Comments on
      The role of appetite-related hormones, adaptive thermogenesis, perceived hunger and stress in long-term weight-loss maintenance: a mixed-methods study.
      ] and subsequent response [
      • Thom G.
      • Dombrowski S.U.
      • Brosnahan N.
      • Algindan Y.Y.
      • Lopez-Gonzalez M.R.
      • Roditi G.
      • et al.
      Response to comments on "The role of appetite-related hormones, adaptive thermogenesis, perceived hunger and stress in long-term weight-loss maintenance: a mixed methods study".
      ] and erratum [
      • Thom G.
      • Dombrowski S.U.
      • Brosnahan N.
      • Algindan Y.Y.
      • Lopez-Gonzalez M.R.
      • Roditi G.
      • et al.
      Correction to: the role of appetite-related hormones, adaptive thermogenesis, perceived hunger and stress in long-term weight-loss maintenance: a mixed-methods study.
      ] from the authors, as the study conclusion stated in the present narrative review is no longer valid.
      Overall, and more importantly, no study has ever reported reduced postprandial fullness after diet-induced weight loss, and my research group has recently shown, in what is likely to be the largest study in this field, that weight loss leads to a sustained increase in postprandial feelings of fullness [
      • Nymo S.
      • Coutinho S.R.
      • Eknes P.H.
      • Vestbostad I.
      • Rehfeld J.F.
      • Truby H.
      • et al.
      Investigation of the long-term sustainability of changes in appetite after weight loss.
      ]. Regardless of the impact of weight loss on appetite, no study has ever shown that increased hunger feelings or ghrelin secretion, or changes in the secretion of satiety peptides, after diet-induced weight loss, increase the risk of weight regain in the long-term.
      Regarding metabolic adaptation, my research group has recently published two important contributions in this field. We have shown that the existence of metabolic adaptation following weight loss is dependent on the energy balance status of the participants, minimal or inexistent when participants are weight stable, and, more importantly, not a driver of relapse in the long-term [
      • Martins C.
      • Roekenes J.
      • Salamati S.
      • Gower B.A.
      • Hunter G.R.
      Metabolic adaptation is an illusion, only present when participants are in negative energy balance.
      ,
      • Martins C.
      • Gower B.A.
      • Hill J.O.
      • Hunter G.R.
      Metabolic adaptation is not a major barrier to weight loss maintenance.
      ]. Lack of standardization of the participants` energy balance status in previous studies is likely to explain the inconsistencies in the literature, regarding the existence or not of metabolic adaptation following weight loss. However, and in line with Bettini et al [
      • Bettini S.
      • Bordigato E.
      • Fabris R.
      • Serra R.
      • Dal Pra C.
      • Belligoli A.
      • et al.
      Modifications of resting energy expenditure after sleeve gastrectomy.
      ], to which the authors refer to in their manuscript, my research group has just published a study showing that metabolic adaptation is associated with less weight and fat mass loss in response to low-energy diets [
      • Martins C.
      • Roekenes J.
      • Gower B.A.
      • Hunter G.R.
      Metabolic adaptation is associated with less weight and fat mass loss in response to low-energy diets.
      ]. So, even though metabolic adaptation is unlikely to be a risk factor for weight regain in the long-term, it might be an important variable in modulating magnitude of weight loss in response to energy-restricted diets [
      • Martins C.
      • Roekenes J.
      • Gower B.A.
      • Hunter G.R.
      Metabolic adaptation is associated with less weight and fat mass loss in response to low-energy diets.
      ] and bariatric surgery [
      • Bettini S.
      • Bordigato E.
      • Fabris R.
      • Serra R.
      • Dal Pra C.
      • Belligoli A.
      • et al.
      Modifications of resting energy expenditure after sleeve gastrectomy.
      ].
      As previously highlighted, there is no single study suggesting that either increased drive to eat or reduced energy expenditure (including metabolic adaptation), which follow weight loss, are drivers of weight regain. My research team has, in fact, showed that the reduction in energy expenditure (at rest and during exercise) and the increased orexigenic drive to eat (ghrelin plasma concentration and hunger feelings) that followed a 17% diet-induced weight loss (with measurements taken outside of ketosis) were not associated with weight regain at 1 year follow-up in a group of men and women with obesity [
      • Nymo S.
      • Coutinho S.R.
      • Rehfeld J.F.
      • Truby H.
      • Kulseng B.
      • Martins C.
      Physiological predictors of weight regain at 1-year follow-up in weight-reduced adults with obesity.
      ].
      Even though the changes in the homeostatic appetite control system, which occur with diet-induced wight loss, are unlikely to be important drivers of relapse, I agree with Busetto et al. that food reward (also known as hedonic appetite control system) is an arena that deserves to be further explored. In the present obesogenic environment most of us live, the homeostatic appetite control system, sensitive to both acute and chronic alterations in nutritional status, is likely to be overridden by food availability and reward. Future research should focus on understanding how weight loss impacts the hedonic appetite control system, aiming at developing better strategies that can be used by reduced-obese individuals in their journey towards a successful long-term weight loss maintenance.

      Declaration of Competing Interest

      The author declares no conflict of interest.

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