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LeptinfMRI - BREVIA Leptin Regulates Striatal Regions and...

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Leptin Regulates Striatal Regions and Human Eating Behavior I. Sadaf Farooqi, 1 * Edward Bullmore, 2 Julia Keogh, 1 Jonathan Gillard, 3 Stephen O Rahilly, 1 Paul C. Fletcher 2 * L eptin is an adipocyte-derived circulating hormone that provides information to the brain about energy stores ( 1 ). The brain s response to leptin involves changes in energy ex- penditure and food intake. Leptin-deficient mam- mals, including humans, are markedly hyperphagic, and leptin replacement reverses this. However, there is little information about how higher brain centers integrate homeostatic signals such as leptin with the rewarding properties of food. We studied a 14- year-old boy (subject 1) and a 19-year-old girl (sub- ject 2) with the very rare condition of congenital leptin deficiency, before and after 7 days of treat- ment with recombinant human leptin ( 2 ). Although no changes in body weight were seen over this time, leptin treatment had a major effect on food intake. Ad libitum energy intake at a test meal was reduced from 152 to 64 kJ/kg of lean mass and from 169 to 98 kJ/kg of lean mass in subjects 1 and 2, respectively [normal ad libitum intake was 54 ± 12 kJ/kg of lean mass (± SD) in age-related controls ( 3 )]. We used functional magnetic resonance imaging (fMRI) to measure differential brain activation by visual images of food compared with images of nonfood in the leptin-deficient and leptin- treated states. We used 10-cm visual analog scores to rate hunger, satiety, and the liking of food images ( 2 ). To examine the interaction with eating, we studied participants in fasted and fed states ( 2 ).
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