Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama, 338-8570, Japan.
Department of Biology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1, Tsushimanaka, Kita-ku, Okayama, 700-8530, Japan.
Sci Rep. 2018 Jun 15;8(1):9176. doi: 10.1038/s41598-018-27458-2.
Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.
胃饥饿素是一种独特的脂肪酸修饰肽激素，在能量平衡和胃肠道动力中具有重要作用。然而，胃饥饿素酰基修饰的中链脂肪酸来源尚不清楚。我们发现，低脂饮食和肠道微生物群的去除并没有降低小鼠胃中酰基胃饥饿素的产生或血浆酰基胃饥饿素水平。RT-PCR 分析显示，涉及脂肪酸合成、代谢和转运的基因在胰腺来源的胃饥饿素瘤 (PG-1) 细胞中表达。用肉毒碱棕榈酰转移酶-1 (CPT-1) 的不可逆抑制剂处理强烈降低了酰化胃饥饿素水平，但不影响 PG-1 细胞中的胃饥饿素或胃饥饿素 o-酰基转移酶 (GOAT) mRNA 水平。我们的结果表明，用于胃饥饿素酰基修饰的中链脂肪酸是由循环中提供的长链脂肪酸通过β-氧化在产生胃饥饿素的细胞自身中产生的。
