The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

被引:127
作者
Grill, H. J. [1 ]
Hayes, M. R. [1 ]
机构
[1] Univ Penn, Philadelphia, PA 19104 USA
关键词
GLP-1; leptin; vagus; caudal brainstem; AMP kinase; GLUCAGON-LIKE PEPTIDE-1; ARTERIAL-BLOOD-PRESSURE; CARDIOVASCULAR RISK-FACTORS; REDUCING MEAL SIZE; GASTRIC DISTENSION; BRAIN-STEM; HEART-RATE; LEPTIN REGULATION; C-FOS; EXENDIN-4;
D O I
10.1038/ijo.2009.10
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
For humans and animal models alike there is general agreement that the central nervous system processing of gastrointestinal (GI) signals arising from ingested food provides the principal determinant of the size of meals and their frequency. Despite this, relatively few studies are aimed at delineating the brain circuits, neurochemical pathways and intracellular signals that mediate GI-stimulation-induced intake inhibition. Two additional motivations to pursue these circuits and signals have recently arisen. First, the success of gastric-bypass surgery in obesity treatment is highlighting roles for GI signals such as glucagon-like peptide-1 (GLP-1) in intake and energy balance control. Second, accumulating data suggest that the intake-reducing effects of leptin may be mediated through an amplification of the intake-inhibitory effects of GI signals. Experiments reviewed show that: (1) the intake-suppressive effects of a peripherally administered GLP-1 receptor agonist is mediated by caudal brainstem neurons and that forebrain-hypothalamic neural processing is not necessary for this effect; ( 2) a population of medial nucleus tractus solitarius (NTS) neurons that are responsive to gastric distention is also driven by leptin; ( 3) caudal brainstem-targeted leptin amplifies the food-intake-inhibitory effects of gastric distention and intestinal nutrient stimulation; (4) adenosine monophosphate-activated protein kinase (AMPK) activity in NTS-enriched brain lysates is elevated by food deprivation and reduced by refeeding and ( 5) the intake-suppressive effect of hindbrain-directed leptin is reversed by elevating hindbrain AMPK activity. Overall, data support the view that the NTS and circuits within the hindbrain mediate the intake inhibition of GI signals, and that the effects of leptin on food intake result from the amplification of GI signal processing. International Journal of Obesity (2009) 33, S11-S15; doi:10.1038/ijo.2009.10
引用
收藏
页码:S11 / S15
页数:5
相关论文
共 63 条
[1]   The inhibitory effects of peripheral administration of peptide YY3-36 and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway [J].
Abbott, CR ;
Monteiro, M ;
Small, CJ ;
Sajedi, A ;
Smith, KL ;
Parkinson, JRC ;
Ghatei, MA ;
Bloom, SR .
BRAIN RESEARCH, 2005, 1044 (01) :127-131
[2]   Leptin regulation of neuroendocrine systems [J].
Ahima, RS ;
Saper, CB ;
Flier, JS ;
Elmquist, JK .
FRONTIERS IN NEUROENDOCRINOLOGY, 2000, 21 (03) :263-307
[3]   Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure [J].
Baggio, LL ;
Huang, QL ;
Brown, TJ ;
Drucker, DJ .
GASTROENTEROLOGY, 2004, 127 (02) :546-558
[4]   Interactions of exendin-(9-39) with the effects of glucagon-like peptide-1-(7-36) amide and of exendin-4 on arterial blood pressure and heart rate in rats [J].
Barragan, JM ;
Rodriguez, RE ;
Eng, J ;
Blazquez, E .
REGULATORY PEPTIDES, 1996, 67 (01) :63-68
[5]   ARTERIAL BLOOD-PRESSURE AND HEART-RATE INDUCED BY GLUCAGON-LIKE PEPTIDE-1-(7-36) AMIDE IN RATS [J].
BARRAGAN, JM ;
RODRIGUEZ, RE ;
BLAZQUEZ, E .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (03) :E459-E466
[6]   Neural contribution to the effect of glucagon-like peptide-1-(7-36) amide on arterial blood pressure in rats [J].
Barragán, JM ;
Eng, J ;
Rodríguez, R ;
Blázquez, E .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1999, 277 (05) :E784-E791
[7]  
Berthoud HR, 1996, ACTA ANAT, V156, P123
[8]   Distribution and structure of vagal afferent intraganglionic laminar endings (IGLEs) in the rat gastrointestinal tract [J].
Berthoud, HR ;
Patterson, LM ;
Neumann, F ;
Neuhuber, WL .
ANATOMY AND EMBRYOLOGY, 1997, 195 (02) :183-191
[9]   Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes [J].
Blonde, L. ;
Klein, E. J. ;
Han, J. ;
Zhang, B. ;
Mac, S. M. ;
Poon, T. H. ;
Taylor, K. L. ;
Trautmann, M. E. ;
Kim, D. D. ;
Kendall, D. M. .
DIABETES OBESITY & METABOLISM, 2006, 8 (04) :436-447
[10]   Exenatide: a GLP-1 receptor agonist as novel therapy for Type 2 diabetes mellitus [J].
Briones, Mariele ;
Bajaj, Mandeep .
EXPERT OPINION ON PHARMACOTHERAPY, 2006, 7 (08) :1055-1064