期刊
REDOX BIOLOGY
卷 47, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2021.102163
关键词
12/15-Lipoxygenase; Xanthine oxidase; Hydrogen peroxide; de novo lipogenesis; Triglyceride biosynthesis; Weight gain
资金
- [HL074860]
- [HL103575]
The study revealed the significant role of 12/15-LOX in high-fat diet-induced weight gain by influencing lipid synthesis and transport, leading to white adipose tissue expansion and increased weight. Modulation of 12/15-LOX metabolism could serve as a potential therapeutic target for weight gain and obesity.
12/15-lipoxygenase (12/15-LOX) plays an essential role in oxidative conversion of polyunsaturated fatty acids into various bioactive lipid molecules. Although 12/15-LOX's role in the pathophysiology of various human diseases has been well studied, its role in weight gain is controversial and poorly clarified. Here, we demonstrated the role of 12/15-LOX in high-fat diet (HFD)-induced weight gain in a mouse model. We found that 12/15-LOX mediates HFD-induced de novo lipogenesis (DNL), triglyceride (TG) biosynthesis and the transport of TGs from the liver to adipose tissue leading to white adipose tissue (WAT) expansion and weight gain via xanthine oxidase (XO)-dependent production of H2O2. 12/15-LOX deficiency leads to cullin2-mediated ubiquitination and degradation of XO, thereby suppressing H2O2 production, DNL and TG biosynthesis resulting in reduced WAT expansion and weight gain. These findings infer that manipulation of 12/15-LOX metabolism may manifest a potential therapeutic target for weight gain and obesity.
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