A new study describes how leptin, an appetite-suppressing hormone released from adipose tissue, is involved in appetite suppression through the dopamine pathway.
Since the discovery of leptin in the 1990s, many questions still remain over how it suppresses appetite. Now, a new study in mice describes novel neurocircuitry between midbrain structures that control feeding behaviours under the modulatory control of leptin.
Leptin links the body and the brain, providing information about its metabolic state and influencing energy balance. Animals deficient for leptin rapidly become obese without its regulatory control of feeding behaviour, showing just how important it is.
“This process is shaped by communication between bodily fat storages (via a hormone called leptin) and the brain’s dopamine reward system. This leptin-dopamine axis is critically important for body weight control, but its modes of action were not well understood,” said Roger Adan, PhD, Department of Translational Neuroscience, University Medical Centre Utrecht.
Not only does leptin suppress eating through signals to brain regions controlling eating behaviours, but it also lowers food’s reward value in the brain’s dopamine (DA) reward system. That food-reward pathway was known to involve dopaminergic neurons of the ventral tegmental area (VTA) signaling to the nucleus accumbens (NAc). However, these DA neurons do not have receptors for leptin.
The researchers mapped the new microcircuitry with a combination of technologies, including optogenetics, chemogenetics and electrophysiology.
“Although leptin receptors are present on [some] dopamine neurons that signal food reward, 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,” said Professor Adan, also of the Department of Translational Neuroscience, University Medical Center Utrecht and University Utrecht.
John Krystal, MD, Editor of Biological Psychiatry, said of the study, “It turns out that leptin plays key modulatory roles in an elegant circuit that unites midbrain and limbic reward circuitry. 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.”
Professor Adan concluded that, “Targeting these neurons may provide a new avenue for the treatment of anorexia nervosa and to support dieting in people with obesity.”
Source: News-Medical.Net
Journal information: Omrani, A., et al. (2021) Identification of novel neurocircuitry through which leptin targets multiple inputs to the dopamine system to reduce food reward seeking. Biological Psychiatry. doi.org/10.1016/j.biopsych.2021.02.017.
