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Sci Rep. 2018 Jun 15;8(1):9176. doi: 10.1038/s41598-018-27458-2.

β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification.

Author information

1
Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama, 338-8570, Japan.
2
Department of Biology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1, Tsushimanaka, Kita-ku, Okayama, 700-8530, Japan.
3
Faculty of Pharmaceutical Sciences, Department of Pharmaceutical and Health Sciences, Josai University, 1-1 Keiyaki dai, Sakado, Saitama, 350-0295, Japan.
4
Research and Development Bureau, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama, 338-8570, Japan.
5
Area of Life-NanoBio, Division of Strategy Research, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama, 338-8570, Japan.
6
Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama, 338-8570, Japan. isakata@mail.saitama-u.ac.jp.

Abstract

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.

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