Table 1.

Effects of leptin replacement therapy on neural plasticity, neural function, and cognition.

	Leptin deficiency due to mutations in the leptin gene	Lipodystrophy	Acquired leptin deficiency
Brain structure	Increases in gray matter concentration in areas associated with regulation of hunger, motor control [14], relay of taste, and hippocampus [15].	Not evaluated.	No changes.
Brain function	Reduced activation of regions linked to hunger and enhanced activation of regions linked to inhibition and satiety, as well as cerebellum [16, 17]. Activation of reward- and food-processing areas [18], with sustained activation effect in the amygdala and in the orbitofrontal cortex, and decrease of the frontopolar cortex activity [19]. Activation in the anteromedial and posterolateral ventral striatum; reduced activation in the nucleus accumbens-caudate and putamen-globus pallidus regions [20]. No change in striatal D2/D3 receptor availability [21].	Increased food-related activity in the orbitofrontal cortex; decreased activity in the amygdala, hippocampus, insula, caudate, and putamen, under postprandial conditions [22].	Acute effects: Increased activation in bilateral insula, dorsolateral prefrontal, and medial frontal cortices in response to viewing food (while fasting). Less activation in the precuneus, middle frontal, thalamic, insular, and parahippocampal cortices (in the fed state). Chronic effects: Increased activation in insular and inferior frontal cortices in response to viewing food (while fasting). Decreased activation in midbrain, cuneus, midcingulate, bilateral parietal, and superior prefrontal cortices (after feeding) [23].
Cognition	Improvements of several subtests within neuropsychological functioning tests [5].	Not evaluated.	Not evaluated.