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Göteborgs universitets publikationer

GLP-1 and weight loss: unraveling the diverse neural circuitry

Författare och institution:
S. E. Kanoski (-); M. R. Hayes (-); Karolina P Skibicka (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 310 ( 10 ) s. R885-R895
ISSN:
0363-6119
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
Glucagon-like peptide-1 (GLP-1) is currently one of the most promising biological systems for the development of effective obesity pharmacotherapies. Long-acting GLP-1 analogs potently reduce food intake and body weight, and recent discoveries reveal that peripheral administration of these drugs reduces food intake largely through humoral pathways involving direct action on brain GLP-1 receptors (GLP-1R). Thus, it is of critical importance to understand the neural systems through which GLP-1 and long-acting GLP-1 analogs reduce food intake and body weight. In this review, we discuss several neural, physiological, cellular and molecular, as well as behavioral mechanisms through which peripheral and central GLP-1R signaling reduces feeding. Particular attention is devoted to discussion regarding the numerous neural substrates through which GLP-1 and GLP-1 analogs act to reduce food intake and body weight, including various hypothalamic nuclei (arcuate nucleus of the hypothalamus, periventricular hypothalamus, lateral hypothalamic area), hindbrain nuclei (parabrachial nucleus, medial nucleus tractus solitarius), hippocampus (ventral subregion; vHP), and nuclei embedded within the mesolimbic reward circuitry [ventral tegmental area (VTA) and nucleus accumbens (NAc)]. In some of these nuclei [VTA, NAc, and vHP], GLP-1R activation reduces food intake and body weight without concomitant nausea responses, suggesting that targeting these specific pathways may be of particular interest for future obesity pharmacotherapy. The widely distributed neural systems through which GLP-1 and GLP-1 analogs act to reduce body weight highlight the complexity of the neural systems regulating energy balance, as well as the challenges for developing effective obesity pharmacotherapies that reduce feeding without producing parallel negative side effects.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper ->
Fysiologi
Nyckelord:
glucagon-like peptide-1, obesity, exendin-4, food reward, liraglutide, Saxenda, Byetta, dipeptidyl, GLUCAGON-LIKE PEPTIDE-1, NUCLEUS-TRACTUS-SOLITARIUS, VENTRAL TEGMENTAL, AREA, CHOLECYSTOKININ-INDUCED SUPPRESSION, CORTICOTROPIN-RELEASING, HORMONE, RECEPTOR-EXPRESSING CELLS, MEDIAL PREFRONTAL CORTEX, PRIMATE, MACACA-MULATTA, CENTRAL-NERVOUS-SYSTEM, REDUCES FOOD-INTAKE
Postens nummer:
238477
Posten skapad:
2016-06-28 11:42

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