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首页> 外文期刊>American Journal of Physiology >Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice
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Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice

机译：餐后通过GPR120通过长链脂肪酸抑制胃饥饿素分泌的过程在分离的胃饥饿素细胞和小鼠中

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Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofiuores-cence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmi-toleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinosi-tol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-7. Quantitative RT-PCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-7 in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion.
机译：Ghrelin是控制食欲和能量稳态的胃肽激素。餐前血浆生长素释放肽水平升高，此后迅速下降。由于直接询问散布在复杂胃黏膜内的生长素释放肽细胞的困难，阻碍了生长素释放肽分泌调节的阐明。因此，我们生成了具有生长素释放肽细胞表达的绿色荧光蛋白（GFP）的转基因小鼠，从而能够表征纯胃分离的表达生长素释放肽的GFP（Ghr-GFP）细胞的生长素释放肽。使用定量RT-PCR和免疫荧光染色，我们检测到长链脂肪酸（LCFA）受体GPR120的高水平表达，而其他LCFA受体GPR40无法检测到。在短期培养的纯Ghr-GFP细胞中，LCFAs二十二碳二烯酸，亚麻酸和棕榈酸-棕榈酸显着抑制了生长素释放肽的分泌。在小鼠中研究了LCFA抑制ghrelin分泌的生理机制。幽门结扎小鼠胃管饲富含LCFA的脂质后，血清生长素释放肽水平被短暂抑制，表明生长素释放肽细胞可直接感觉到摄入的腔内脂质引起的胃LCFA升高。通过测量组织摄取LCFA，脂蛋白脂肪酶（LPL），脂肪酸转位酶（CD36），糖基磷脂酰肌醇-tol锚定的HDL结合蛋白1和核脂肪酸的标志物来评估餐食引起的胃粘膜LCFA的增加受体过氧化物酶体增殖物激活受体7。定量RT-PCR研究表明，餐后胃粘膜中脂蛋白脂肪酶，糖基磷脂酰肌醇锚定的HDL结合蛋白1和过氧化物酶体增殖物激活受体7的mRNA水平显着增加。这些结果表明，与膳食相关的胃粘膜LCFA的增加与生长素释放肽细胞上的GPR120相互作用，从而抑制生长素释放肽的分泌。

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