Ninety years ago, an editorial in JAMA questioned the prevailing approach to obesity treatment: “When we read that ‘the fat woman has the remedy in her own hands—or rather between her own teeth’ . . . there is an implication that obesity is usually merely the result of unsatisfactory dietary bookkeeping. . . [Although logic suggests that body fat] may be decreased by altering the balance sheet through diminished intake, or increased output, or both . . . [t]he problem is not really so simple and uncomplicated as it is pictured.”1 Since then, billions of dollars have been spent on research into the biological factors affecting body weight, but the near-universal remedy remains virtually the same, to eat less and move more. According to an alternative view, chronic overeating represents a manifestation rather than the primary cause of increasing adiposity. Attempts to lower body weight without addressing the biological drivers of weight gain, including the quality of the diet, will inevitably fail for most individuals. This Viewpoint summarizes the evidence for this seemingly counterintuitive hypothesis, versions of which have been debated for more than a century.2
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