Leptin reverses weight loss–induced changes in regional neural activity responses to visual food stimuli

Abstract

Increased hunger and food intake during attempts to maintain weight loss are a critical problem in clinical management of obesity.To determine whether reduced body weight maintenance is accompanied by leptinsensitive changes in neural activity in brain regions affecting regulatory and hedonic aspects of energy homeostasis, we examined brain region-specific neural activity elicited by food-related visual cues using functional MRI in 6 inpatient obese subjects.Subjects were assessed at their usual weight and, following stabilization at a 10% reduced body weight, while receiving either twice daily subcutaneous injections of leptin or placebo.Following weight loss, there were predictable changes in neural activity, many of which were reversed by leptin, in brain areas known to be involved in the regulatory, emotional, and cognitive control of food intake.Specifically, following weight loss there were leptin-reversible increases in neural activity in response to visual food cues in the brainstem, culmen, parahippocampal gyrus, inferior and middle frontal gyri, middle temporal gyrus, and lingual gyrus.There were also leptin-reversible decreases in activity in response to food cues in the hypothalamus, cingulate gyrus, and middle frontal gyrus.These data are consistent with a model of the weightreduced state as one of relative leptin deficiency.Nonstandard abbreviations used: BOLD, blood oxygen level-dependent; fMRI, functional MRI; Wtinitial, initial body weight; Wt-10%leptin, weight approximately 10% below Wtinitial with twice daily injections of recombinant methionyl human leptin; Wt-10%placebo, weight approximately 10% below Wtinitial with twice daily injections of placebo.