Editors' ChoiceObesity

Yo-Yo Dieting: Biology or Behavior?

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Science Translational Medicine  09 Nov 2011:
Vol. 3, Issue 108, pp. 108ec180
DOI: 10.1126/scitranslmed.3003403

Losing weight is tough, and although caloric restriction is effective in the short term, many dieters find it nearly impossible to sustain weight loss. So for the nearly 1.5 billion individuals worldwide who are overweight or obese, yo-yo dieting becomes a way of life. Now, Sumithran and colleagues offer new insight into the complex hormonal regulation of body weight and identify trends that might offer a physiological rather than a behavioral explanation for the inability to maintain weight loss.

Regulation of food intake and energy expenditure is controlled by a dizzying (and growing) number of hormones and circuits that encompass the brain, gut, pancreas, and adipose tissue. In order to dissect these relationships in a human cohort, Sumithran et al. studied volunteers with a body mass index (BMI) between 27 and 40 kg/m2 who consumed a very-low-calorie diet—500 to 550 kcal/day—for 8 weeks. Over the next 2 weeks, an ordinary diet was gradually reintroduced, and study participants were given individual counseling and a plan for weight maintenance. By week 10 of the study, participants lost an average of 14% of their initial body weights. However, the average sustained weight loss among subjects at week 62 was only 8% of initial body weight. Fasting and post-meal serum concentrations of the metabolic hormones ghrelin, glucagon-like peptide–1 (GLP-1), gastric inhibitory peptide (GIP), pancreatic polypeptide, amylin, insulin, leptin, cholecystokinin, and peptide YY were measured at baseline, 10, and 62 weeks, and subjective hunger was rated at each time point.

Secretion of hormones that suppress appetite such as leptin, peptide YY, and cholecystokinin fell and remained low up to 12 months after weight loss. Furthermore, secretion of hormones that promote eating and energy storage, such as ghrelin and GIP, increased and remained elevated over this same time period. These changes coincided with subjective feelings of hunger that persisted for up to a year after weight loss, suggesting that voluntary weight loss is opposed by a number of powerful biological and compensatory mechanisms that encourage weight regain. As rising rates of obesity threaten to overwhelm our public health resources, the challenge will be to translate these findings into effective pharmacological treatments that promote permanent weight loss and end yo-yo dieting.

P. Sumithran et al., Long-term persistence of hormonal adaptations to weight loss. N. Engl. J. Med. 365, 1597–1604 (2011). [PubMed]

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