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Publication Information


Kim, K.S. et al.


Enhanced Hypothalamic Leptin Signaling in Mice Lacking Dopamine D2 Receptors

J. Biol. Chem. 285(12): 8905-8917


Obesity is a major problem worldwide. Once considered an affliction of those with no willpower, scientists now understand that there are biological mechanisms underlying overeating and obesity. Many researchers have studied the role of the dopaminergic pathway (the projection from the ventral tegmental area to the nucleus accumbens) in feeding behavior. For instance, the Johnson and Kenny paper presents a series of results that support a role of the dopamine reward circuit in binge eating. However, it is difficult to argue that the hypo-function of the reward circuit directly causes/underlies obesity. Eating certainly triggers various brain receptors, but food also impacts the metabolic hormones, such as leptin and ghrelin. Thus, the Kim et al. paper attempts to forge a link between the metabolic hormone leptin and a reward-related neurotransmitter - dopamine.

Scientific Question

Although researchers have primarily concentrated on the regulation of feeding behavior by dopaminergic neurons in the reward system (the pathway from the ventral tegmental area to the nucleus accumbens), in this article, Kim et al. question whether hypothalamic signaling can modulate energy homeostasis.

Primary Hypothesis

Based on observations that dopamine D2 receptor knock-out mice (D2R-/-) have reduced body weight and food intake compared to age-matched wild type (WT) littermates and that such mice have enhanced leptin sensitivity, Kim et al. hypothesize that there is an inhibitory interaction between dopamine and D2Rs and leptin signaling in the hypothalamus.

Click on the terms below for a brief definition of the technique, as well as a description of its use in the Kim et al. paper.

Evaluation of Food Intake and Body Composition
Intracerebroventricular (i.c.v.) Cannulation
Pair Feeding
Western Blots
Indirect Calorimetry
Luciferase Reporter Gene Assay
In Situ Hybridization
Real Time Polymerase Chain Reaction (RT-PCR)

Conclusions and Critique

Proceed to Figure 1.
Return to the project home page Neural Reward, Energy Homeostasis, and Addiction-like Compulsive Eating.

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