Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

被引:48
作者
Kohno, Daisuke [1 ,2 ]
Koike, Miho [1 ]
Ninomiya, Yuzo [3 ,4 ]
Kojima, Itaru [5 ]
Kitamura, Tadahiro [2 ]
Yada, Toshihiko [6 ]
机构
[1] Gunma Univ, Adv Sci Res Leaders Dev Unit, Maebashi, Gunma, Japan
[2] Gunma Univ, Inst Mol & Cellular Regulat, Metab Signal Res Ctr, Maebashi, Gunma, Japan
[3] Kyushu Univ, Res & Dev Ctr Taste & Odor Sensing, Div Sensory Physiol, Fukuoka, Japan
[4] Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA
[5] Gunma Univ, Inst Mol & Cellular Regulat, Dept Cell Biol, Maebashi, Gunma, Japan
[6] Jichi Med Univ, Sch Med, Dept Physiol, Div Integrat Physiol, Shimotsuke, Japan
关键词
feeding; sweet taste receptor; sucralose; glucose; leptin; POMC; NEUROPEPTIDE-Y; PROOPIOMELANOCORTIN NEURONS; SIGNALING SYSTEMS; GHRELIN; HOMEOSTASIS; SUCRALOSE; INTEGRATION; PATTERNS; BEHAVIOR; POMC;
D O I
10.3389/fnins.2016.00502
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+](i)) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10-5-10-2 M dose dependently increased [Ca2+](i) in 12-16% of ARC neurons. The sucralose-induced [Ca2+](i) increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+](i), increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation mainly occurs on non-POMC leptin-responding neurons and contributes to glucose responding. Endogenous sweet molecules including glucose may regulate energy homeostasis through sweet taste receptors on glucose-and leptin-responsive neurons in the ARC.
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页数:11
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