期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 37, 期 7-9, 页码 417-436出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2021.0190
关键词
vertebrates; Mn; oxidative stress; lipid metabolism; deacetylation; molecular nutrition
资金
- National Key Research and Development Program of China [2018YFD0900400]
- National Natural Science Foundation of China [31872585]
High dietary Mn intake promotes lipid deposition in the intestine through the oxidative stress-SIRT1-PPARγ pathway.
Aims: Excessive manganese (Mn) exposure is toxic, and induces lipid deposition, but the underlying mechanisms remain elusive. Herein, we explored how dietary Mn supplementation affects lipid deposition and metabolism in the intestine of vertebrates using the yellow catfish Pelteobagrus fulvidraco as the model.Results: High-Mn (H-Mn) diet increased intestinal Mn content, promoted lipid accumulation and lipogenesis, and inhibited lipolysis. In addition, it induced oxidative stress, upregulated metal-response element-binding transcription factor-1 (MTF-1), and peroxisome proliferator-activated receptor gamma (PPAR gamma) protein expression in the nucleus, induced PPAR gamma acetylation, and the interaction between PPAR gamma and retinoid X receptor alpha (RXR alpha), while it downregulated sirtuin 1 (SIRT1) expression and activity. Mechanistically, Mn activated the MTF-1/divalent metal transporter 1 (DMT1) pathway, increased Mn accumulation in the mitochondria, and induced oxidative stress. This in turn promoted lipid deposition via deacetylation of PPAR gamma at K339 by SIRT1. Subsequently, PPAR gamma mediated Mn-induced lipid accumulation through transcriptionally activating fatty acid translocase, stearoyl-CoA desaturase 1, and perilipin 2 promoters.Innovation: These studies uncover a previously unknown mechanism by which Mn induces lipid deposition in the intestine via the oxidative stress-SIRT1-PPAR gamma pathway.Conclusion: High dietary Mn intake activates MTF-1/DMT1 and oxidative stress pathways. Oxidative stress-mediated PPAR gamma deacetylation at K339 site contributes to increased lipid accumulation. Our results provided a direct link between Mn and lipid metabolism via the oxidative stress-SIRT1-PPAR gamma axis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据