Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 106, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2022.109032
Keywords
Ether-phospholipids; High-fat diet; Hypothalamic autophagy; alpha-MSH; Metabolic syndrome
Funding
- National Key R&D Program of China [2018YFC0311201]
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This study demonstrates that dietary ether-phospholipids (ether-PLs) can alleviate high-fat diet-induced hepatic lipid accumulation and regulate hypothalamic autophagy. Ether-PLs activate autophagy in the hypothalamus, which helps maintain energy balance and ameliorate the effects of chronic high-fat diet-induced obesity.
As a promising group of natural bioactive lipids, ether-phospholipids (ether-PLs), exhibit the ability to attenuate high-fat diet (HFD)-induced lipid accumulation and atherosclerosis. However, the underlying mechanism is unclear. Autophagy has been implicated in the regulation of obesity. Therefore, we investigated the effects of dietary ether-PLs on hepatic steatosis and the activation of hypothalamic autophagy. HFD-fed C57BL/6J mice were orally administered with ether-PLs (150 mg/kg body weight) including plasmenyl phosphatidylethanolamine (PE-P) and plasmanyl phosphatidylcholine (PC-O) for three days or eight weeks. Ether-PLs supplementation relieved diet-induced hepatic lipid accumulation and regulated the hypothalamic peroxisome proliferator-activated receptor gamma (PPAR gamma) and CD36. Notably, PE-P activated hypothalamic autophagy more strongly than PC-O, with an increased ratio of microtubule-associated protein light chain 3 II/I (LC3II/I) and reduced p62/sequestosome-1 (p62) accumulation by rescuing the HFD-impaired autophagylysosome fusion. The phosphorylation of ULK1 mediated by Akt-mTOR and AMPK, was involved in ether-PLs activated autophagy. Furthermore, the enhanced hypothalamic autophagy promoted the production of alpha-melanocyte-stimulating hormone (alpha-MSH), which has been reported to maintain energy balance. It is concluded that ether-PLs ameliorated HFD-induced hypothalamic autophagy and ameliorated hepatic steatosis. Ether-PLs could thus be an attractive autophagy-enhancers against chronic HFD-induced obesity.(C) 2022 Elsevier Inc. All rights reserved.
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