GPR40 and GPR120 fatty acid sensors are critical for postoral but not oral mediation of fat preferences in the mouse
GPR40 and GPR120 fatty acid sensors are critical for postoral but not oral mediation of fat preferences in the mouse
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DOI：
10.1152/ajpregu.00440.2013
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发表时间：
2013-12-01
影响因子：
2.8
通讯作者：
Ackroff, Karen
中科院分区：
文献类型：
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作者：
Sclafani, Anthony;Zukerman, Steven;Ackroff, Karen
除了口腔感觉信号外，脂肪的后作用还会刺激食欲并调节风味偏好，但介导这些反应的肠道传感器尚不清楚。在这里，我们研究了脂肪酸传感器 GPR40 和 GPR120 在对大豆油乳剂 (Intralipid) 的后口和口腔偏好中的作用。训练小鼠饮用一种与胃内（IG）油输液搭配的调味溶液（CS+），以及与输注水搭配的另一种调味溶液（CS+）。缺失 GPR40 或 GPR120 传感器的敲除 (KO) 小鼠在一瓶测试（1 小时/天）中增加了 CS+ 摄入量，但低于野生型 (WT) 小鼠。在两瓶测试中，KO 小鼠也比 CS- 更喜欢 CS+，但这种偏好在 GPR40 KO 小鼠中减弱。同时缺失 GPR40 和 GPR120 的双敲除 (DoKO) 小鼠表现出对 CS+ 摄入的刺激减弱，并且仅有边际的 CS+ 偏好。在每天 24 小时的测试中，DoKO 小鼠产生了更明显的 CS+ 偏好，尽管比 WT 小鼠弱。 DoKO 小鼠消耗的 CS+ 与 IG Intralipid 配对的量也较少，并且口服测试中的 Intralipid 也较少。然而，DoKO 小鼠（如 GPR40 KO 和 GPR120 KO 小鼠）与 WT 小鼠相比，对浓度为 0.001%-20% 浓度的英脱利匹特而非水的偏好没有差异。与先前在缺失 CD36 脂肪酸传感器的小鼠中获得的结果相反，这些发现表明，GPR40 和 GPR120 一起在脂肪对食欲的后刺激中发挥着关键作用，但对于口腔脂肪偏好而言并不是必需的。
In addition to orosensory signals, postoral actions of fat stimulate appetite and condition flavor preferences, but the gut sensors mediating these responses are unknown. Here, we investigated the role of the fatty acid sensors GPR40 and GPR120 in postoral and oral preferences for a soybean oil emulsion (Intralipid). Mice were trained to drink a flavored solution (CS+) paired with intragastric (IG) oil infusions and another flavored solution (CS+) paired with water infusions. Knockout (KO) mice missing GPR40 or GPR120 sensors increased their CS+ intake in one-bottle tests (1 h/day) but less so than wild-type (WT) mice. The KO mice also preferred the CS+ to CS- in a two-bottle test, but the preference was attenuated in GPR40 KO mice. Double-knockout (DoKO) mice missing both GPR40 and GPR120 displayed attenuated stimulation of CS+ intake and only a marginal CS+ preference. The DoKO mice developed a more substantial CS+ preference when tested 24 h/day, although weaker than that of WT mice. The DoKO mice also consumed less of the CS+ paired with IG Intralipid, as well as less Intralipid in oral tests. However, DoKO mice, like GPR40 KO and GPR120 KO mice did not differ from WT mice in their preference for Intralipid over water at 0.001%-20% concentrations. In contrast to prior results obtained with mice missing the CD36 fatty acid sensor, these findings indicate that, together, GPR40 and GPR120 play a critical role in the postoral stimulation of appetite by fat but are not essential for oral fat preferences.