Oral administration of trehangelin-A alleviates metabolic disorders caused by a high-fat diet through improvement of lipid metabolism and restored beneficial microbiota

Hiroki Ishikawa*, Satoshi Ino, Takuji Nakashima, Hirotaka Matsuo, Yōko Takahashi, Chikara Kohda, Satoshi Ōmura, Masayuki Iyoda, Kazuo Tanaka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The present study investigated whether or not the oral administration of trehangelin-A (THG-A) is effective for metabolic disorders caused by a high-fat diet, as we previously showed that the intraperitoneal administration of THG-A improved metabolic disorders caused by a high-fat diet. Mice received a control diet or high-fat diet for eight weeks. Concurrently, mice were orally administered 0.2 ml/mouse phosphate-buffered saline (PBS) or 1 or 10 mg/0.2 ml/mouse of THG-A once daily during the experiment. The weight gain caused by a high-fat diet was significantly suppressed by oral THG-A compared to a high-fat diet without THG-A. In addition, at eight weeks after starting the diet, the increased plasma total-cholesterol (T-CHO) and low-density lipoprotein-cholesterol (LDL-C) levels caused by a high-fat diet were significantly reduced by 10 mg/mouse THG-A and tended to attenuated by 1 mg/mouse THG-A. The LDL receptor and CYP7A1 mRNA expression in liver associated with lipid metabolism for reducing plasma LDL-C levels was significantly enhanced by oral THG-A. In contrast, oral THG-A exerted no marked effects on mice fed the control diet. The dysbiosis of a high-fat diet fed mice, which is in the form of an increased Firmicutes-to-Bacteroidetes ratio, also recovered, and the high-fat diet induced decreased levels of Bacteroides and Akkermansia genera, which are beneficial microbiota against metabolic disorders, were also restored by oral THG-A. These results indicate that oral THG-A administration acts on metabolic disorders by improving the lipid metabolism and restoring beneficial microbiota to resolve high-fat diet induced dysbiosis.

Original languageEnglish
Pages (from-to)360-367
Number of pages8
JournalObesity Research and Clinical Practice
Volume14
Issue number4
DOIs
Publication statusPublished - 2020 Jul 1
Externally publishedYes

Keywords

  • Gut microbiota
  • High-fat diet
  • Lipid metabolism
  • Trehangelin-A (THG-A)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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