CART peptides: regulators of body weight, reward and other functions

• Published in: Nature reviews. Neuroscience Vol. 9; no. 10; pp. 747 - 758
• Main Authors: Kuhar, M. J, Rogge, G, Jones, D, Hubert, G. W, Lin, Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2008; Nature Publishing Group
• Subjects: Affective Symptoms - genetics; Affective Symptoms - metabolism; Affective Symptoms - physiopathology; Amino acids; Amphetamines; Animal Genetics and Genomics; Animals; Appetite Regulation - physiology; Behavioral Sciences; Biological and medical sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Body weight; Body Weight - physiology; Central Nervous System - anatomy & histology; Central Nervous System - metabolism; Cocaine; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Genetic regulation; Humans; Messenger RNA; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurobiology; Neurosciences; Peptides; Physiological aspects; Physiology; Receptors, Cell Surface - metabolism; review-article; Reward; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: nervous system and sense organs; United States; Hormone; Peptides; Central nervous system; Information processing; Neurotransmitter; Amfetamine; Review; Reward; Biological receptor
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/nrn2493

Key Points
The CART (cocaine- and amphetamine-regulated transcript) gene, transcripts and peptides were discovered through the initial observation that psychostimulant drugs elevated the levels of the CART mRNA. Although the full name reflects this particular effect, CART peptides are involved in more processes than just those that mediate the effects of drugs like cocaine.
CART mRNA is transcribed by the action of known transcription factors, such as cyclic AMP-response-element-binding protein (CREB), and the CART propeptide is processed into smaller active fragments by prohormone convertases.
CART peptides are neurotransmitters and neurohormones that are widely but discretely distributed throughout the brain and the periphery.
The CART peptide receptor (although it is possible that there is more than one) is thought to be a G-protein-coupled receptor that signals through inhibitory (G
i/o
) mechanisms.
There has been much interest in CART peptides as regulators of body weight. Evidence for this role comes from both animal and human studies.
CART peptides, when injected into the nucleus accumbens, reduce the actions of psychostimulant drugs like cocaine. It has been proposed that CART peptides modulate the effects of cocaine.
Many experiments suggest that CART peptides also play a part in endocrine regulation, stress, anxiety and depression, cardiovascular function, pain and other processes.
Because CART peptides have so many effects, including a major role in body weight regulation, the CART system could be an interesting target for drug development.
Since their discovery as factors that were upregulated by psychostimulant drugs, CART peptides have emerged as major neurotransmitters and hormones. Here, Kuhar and colleagues provide an overview of the various effects of CART peptides.
Over the past decade or so, CART (cocaine- and amphetamine-regulated transcript) peptides have emerged as major neurotransmitters and hormones. CART peptides are widely distributed in the CNS and are involved in regulating many processes, including food intake and the maintenance of body weight, reward and endocrine functions. Recent studies have produced a wealth of information about the location, regulation, processing and functions of CART peptides, but additional studies aimed at elucidating the physiological effects of the peptides and at characterizing the CART receptor(s) are needed to take advantage of possible therapeutic applications.