Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism

Ming Liang Lee, Hirokazu Matsunaga, Yuki Sugiura, Takahiro Hayasaka, Izumi Yamamoto, Taiga Ishimoto, Daigo Imoto, Makoto Suematsu, Norifumi Iijima, Kazuhiro Kimura, Sabrina Diano, Chitoku Toda

研究成果: Article査読

抄録

The hypothalamus plays a central role in monitoring and regulating systemic glucose metabolism. The brain is enriched with phospholipids containing poly-unsaturated fatty acids, which are biologically active in physiological regulation. Here, we show that intraperitoneal glucose injection induces changes in hypothalamic distribution and amounts of phospholipids, especially arachidonic-acid-containing phospholipids, that are then metabolized to produce prostaglandins. Knockdown of cytosolic phospholipase A2 (cPLA2), a key enzyme for generating arachidonic acid from phospholipids, in the hypothalamic ventromedial nucleus (VMH), lowers insulin sensitivity in muscles during regular chow diet (RCD) feeding. Conversely, the down-regulation of glucose metabolism by high fat diet (HFD) feeding is improved by knockdown of cPLA2 in the VMH through changing hepatic insulin sensitivity and hypothalamic inflammation. Our data suggest that cPLA2-mediated hypothalamic phospholipid metabolism is critical for controlling systemic glucose metabolism during RCD, while continuous activation of the same pathway to produce prostaglandins during HFD deteriorates glucose metabolism.

本文言語English
論文番号2330
ジャーナルNature communications
12
1
DOI
出版ステータスPublished - 2021 12

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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