Leptin Regulates Striatal Regionsand Human Eating BehaviorI. Sadaf Farooqi,1* Edward Bullmore,2Julia Keogh,1Jonathan Gillard,3Stephen O’Rahilly,1Paul C. Fletcher2*Leptin is an adipocyte-derived circulatinghormone that provides information to thebrain about energy stores (1). The brain’sresponse 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, thereis little information about how higher brain centersintegrate homeostatic signals such as leptin withthe 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 congenitalleptin deficiency, before and after 7 days of treat-ment with recombinant human leptin (2). Althoughno changes in body weight were seen over thistime, leptin treatment had a major effect on foodintake. Ad libitum energy intake at a test meal wasreduced from 152 to 64 kJ/kg of lean mass andfrom 169 to 98 kJ/kg of lean mass in subjects 1 and2, respectively [normal ad libitum intake was 54 ±12 kJ/kg of lean mass (± SD) in age-related controls(3)]. We used functional magnetic resonanceimaging (fMRI) to measure differential brainactivation by visual images of food compared withimages of nonfood in the leptin-deficient and leptin-treated states. We used 10-cm visual analog scoresto rate hunger, satiety, and the“liking”of foodimages (2). To examine the interaction with eating,we studied participants in fasted and fed states (2).
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