A study by researchers from the University Medical Center Utrecht and University Utrecht, the Netherlands, has reported novel neurocircuitry between the midbrain structures that control feeding behaviours are under modulatory control by leptin. The findings were reported in the study, ‘Identification of novel neurocircuitry through which leptin targets multiple inputs to the dopamine system to reduce food reward seeking’, was published in Biological Psychiatry.
Leptin acts as a critical link between the body and the brain, providing information about metabolic state and exerting control over energy balance. The importance of leptin is illustrated by the finding that animals deficient for leptin rapidly become obese without its regulatory stop on feeding behaviour. However, the exact point of leptin action to modulate motivation for a food reward is unknown.
“This process is shaped by communication between bodily fat storages (via a hormone called leptin) and the brain's dopamine reward system,” explained Dr Roger Adan of the Department of Translational Neuroscience, University Medical Center Utrecht and University Utrecht, who led the study. “This leptin-dopamine axis is critically important for body weight control, but its modes of action were not well understood.”
Leptin suppresses eating by signalling to brain regions that control eating behaviors, but it also decreases the reward value inherent in foods, engaging the brain's dopamine (DA) reward system. That food-reward pathway was known to involve dopaminergic neurons of the ventral tegmental area (VTA) signalling to the nucleus accumbens (NAc), but most of those DA neurons do not contain receptors for leptin. The work used a combination of optogenetics, chemogenetics and electrophysiology to map the new microcircuitry.
"Although leptin receptors are present on [some] dopamine neurons that signal food reward," added Adan, “We discovered that leptin receptors are also present on inhibitory neurons that more strongly regulate the activity of dopamine neurons. Some of these inhibitory neurons suppressed food seeking when [animals were] hungry, whereas others [did so] only when [animals were] in a sated state. Targeting these neurons may provide a new avenue for the treatment of anorexia nervosa and to support dieting in people with obesity."
"It turns out that leptin plays key modulatory roles in an elegant circuit that unites midbrain and limbic reward circuitry,” explained Dr John Krystal, Editor of Biological Psychiatry. "By inhibiting hypothalamic neurons and ultimately suppressing the activity of dopamine neurons in the midbrain that signal reward and promote feeding, leptin reduces food intake in animals under conditions when caloric intake has exceeded energy use."