Leptin puts the brake on food intake via a new nerve circuit

Philadelphia, April 6, 2021 – Since the discovery of the hormone leptin in the 1990s, researchers have wondered, how does leptin, a hormone produced by body fat, suppress appetite? Despite the colossal gains in the intervening three decades, many questions remain. Now, a new study in mice describes novel neural circuits between midbrain structures that control feeding behaviors that are moderately controlled by leptin. The study shows in Biological PsychiatryPublished by Elsevier.

“In non-obese animals, leptin stops overeating,” said John Crystal, editor of Biological Psychiatry, of the results.

Leptin acts as an important link between the body and the brain, providing information about metabolic state and exercising control over energy balance. The importance of leptin is illustrated by the discovery that animals deficient in the hormone leptin become obese rapidly without their regulatory disruption of feeding behavior.

Roger Adan, Ph.D., from the Department of Transitional Neuroscience, University Medical Center in Utrecht and the University of Utrecht, the Netherlands, who led the study, said: “This process is shaped by the communication between fat stores in the body (via a hormone called leptin) and the dopamine reward system in the brain. The leptin-dopamine axis is extremely important for controlling body weight, but its modes of action were not well understood.

Leptin prevents eating by sending signals to areas of the brain that control eating behaviors, but it also reduces the reward value inherent in foods, thereby engaging the dopamine reward system (DA) in the brain. The food reward pathway was known to involve dopaminergic neurons in the ventral tegmental area (VTA) indicating the nucleus accumbens (NAc), but most DA neurons do not contain leptin receptors.

The work used a range of powerful techniques, including optogenetics, chemical genetics, and electrophysiology to map new microcircuits.

Although there is a leptin receptor [some] Professor Adan, from the Department of Transitional Neuroscience and University Medical Center in Utrecht and Utrecht University, said, “We have discovered that leptin receptors are also present in inhibitory neurons that regulate dopamine neuron activity more strongly. Some of these inhibitory neurons suppress the search for food when [animals were] Hungry, while the others [did so] Just when [animals were] In a state of glut. “

Of the study, Dr. Crystal said, “It turns out that leptin plays major modifying roles in an elegant circuit that unifies the midbrain and limbic reward circuit. By inhibiting neurons in the hypothalamus and suppressing the activity of dopamine neurons in the midbrain that signal reward and enhance nutrition, Leptin reduces food intake in animals under conditions where caloric intake exceeds energy use. ”

Ultimately, Professor Adan said, “Targeting these neurons may provide a new way to treat anorexia nervosa and support dieting for obese people.”


Notes to Editors

The article is “Identifying New Neural Circuits Through Which Leptin Targets Multiple Inputs to the Dopamine System to Reduce the Pursuit of Nutritional Reward” by Azar Amrani, Veron de Friend, Bart Lauder, Iris Stoltenberg, Karlin Coyge, Inge Wolterink-Doncellar, Minnicky Luigendijk-Berg, Keith Garner, Lisan Van Te Saint, Animic Roseboom, Susan Dickson, Frank May, Roger Adan ( /10.1016 /J.Biopsy.2021.02.017). Appear as an article in Press in Biological PsychiatryPublished by Elsevier.

Copies of this paper are available to accredited journalists upon request. Please contact Rhiannon Bugno at [email protected]“>[email protected] Or +1 254 522 9700. Journalists wanting to interview the authors can contact Roger Adan at [email protected]“>[email protected] Or +31 88 756 8517.

Authors’ affiliations, financial disclosures, and conflicts of interest are provided in the article.

Crystal John H. Crystal, MD, is the chair of the department of psychiatry at Yale University School of Medicine, chair of psychiatry at Yale-New Haven Hospital, and a research psychiatrist in the health care system in Connecticut. His financial disclosures and conflicts of interest are available here.

About Biological Psychiatry

Biological Psychiatry It is the official journal of the Society of Biological Psychiatry, and its purpose is to promote excellence in scientific research and education in areas that research the nature, causes, mechanisms, and treatment of disorders of thought, emotion, or behavior. In line with this assignment, this international peer-reviewed journal publishes essential and clinical contributions from all disciplines and research areas related to pathophysiology and treatment of major mental disorders.

The journal publishes new findings of original research that represent significant new leadership or influence in the field, particularly those that address genetic and environmental risk factors, neurocircuits and neurochemistry, and important new treatment approaches Reviews and comments that focus on current research topics and concerns are also encouraged.

Biological Psychiatry It is one of the most selective and cited journals in the field of neuropsychology. It ranks 7thThe tenth Out of 155 psychiatry titles and 12The tenth Of the 271 neuroscience titles in Journal Citations Reports® published by Clarivate Analytics. The 2019 Biological Psychiatry Impact Factor Score is 12095. http: // www.Sup.Deer /magazine

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Media contact

Rhiannon Bogno, editorial office

Biological Psychiatry

+1 254 522 9700

[email protected]

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