Leptin regulates energy balance and motivation through action at distinct neural circuits.

Abstract:

BACKGROUND:Overconsumption of calorically dense foods contributes substantially to the current obesity epidemic. The adiposity hormone leptin has been identified as a potential modulator of reward-induced feeding. The current study asked whether leptin signaling within the lateral hypothalamus (LH) and midbrain is involved in effort-based responding for food rewards and/or the modulation of mesolimbic dopamine. METHODS:The contribution of endogenous leptin signaling for food motivation and mesolimbic dopamine tone was examined after viral-mediated reduction of the leptin receptor within LH and midbrain neurons in male rats. RESULTS:Knockdown of leptin receptors selectively in the LH caused increased body weight, caloric consumption, and body fat in rats maintained on a calorically dense diet. Knockdown of leptin receptors selectively in midbrain augmented progressive ratio responding for sucrose and restored high-fat, diet-induced suppression of dopamine content in the nucleus accumbens. CONCLUSIONS:In summary, endogenous leptin signaling in the hypothalamus restrains the overconsumption of calorically dense foods and the consequent increase in body mass, whereas leptin action in the midbrain regulates effort-based responding for food rewards and mesolimbic dopamine tone. These data highlight the ability of leptin to regulate overconsumption of palatable foods and food motivation through pathways that mediate energy homeostasis and reward, respectively.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Davis JF,Choi DL,Schurdak JD,Fitzgerald MF,Clegg DJ,Lipton JW,Figlewicz DP,Benoit SC

doi

10.1016/j.biopsych.2010.08.028

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

668-74

issue

7

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(10)00912-1

journal_volume

69

pub_type

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