期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 298, 期 9, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jbc.2022.102322
关键词
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资金
- JSPS KAKENHI [JP16K21318]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan, Jichi Medical University Young Investigator Award
- Astellas Pharma
- Daiichi Sankyo Co
- Ono Pharma
- Shionogi Co
- Boehringer Ingelheim Japan
- Kowa
- Co
- Ono Pharma
- Mitsubishi Tanabe Pharma
- Takeda Pharma Co
- Toyama Chemical Co
- Teijin
- Sumitomo Dainippon Pharma
- Sano fi K.K.
- Novo Nordisk Pharma
- MSD K.K.
- Pfizer Japan
- Novartis Pharma
- Eli Lilly Co
- NHLBI
- National Institutes of Health (USA)
- [HL45095]
- [73029]
During obesity, tissue macrophages increase in number and become proinflammatory, contributing to metabolic dysfunction. The role of macrophage-derived LPL in adipose tissue remodeling and lipoprotein metabolism is largely unknown. This study found that the loss of myeloid LPL led to extensive fibrosis of adipose tissue and hypertriglyceridemia.
During obesity, tissue macrophages increase in number and become proinflammatory, thereby contributing to metabolic dysfunction. Lipoprotein lipase (LPL), which hydrolyzes triglyceride in lipoproteins, is secreted by macrophages. However, the role of macrophage-derived LPL in adipose tissue remodeling and lipoprotein metabolism is largely unknown. To clarify these issues, we crossed leptin-deficient Lep(ob/ob) mice with mice lacking the Lpl gene in myeloid cells (Lpl(m-/m-)) to generate Lpl(m-/m-);Lep(ob/ob) mice. We found the weight of per-igonadal white adipose tissue (WAT) was increased in Lpl(m-/m-);Lep(ob/ob) mice compared with Lep(ob/ob) mice due to substantial accumulation of both adipose tissue macrophages and collagen that surrounded necrotic adipocytes. In the fibrotic epidydimal WAT of Lpl(m-/m-);Lep(ob/ob) mice, we observed an increase in collagen VI and high mobility group box 1, while alpha-smooth muscle cell actin, a marker of myofibroblasts, was almost undetectable, suggesting that the adipocytes were the major source of the collagens. Furthermore, the adipose tissue macrophages from Lpl (m-/m-);Lep(ob/ob) mice showed increased expression of genes related to fibrosis and inflammation. In addition, we determined Lpl (m-/m-);Lep(ob/ob) mice were more hypertriglyceridemic than Lep(ob/ob) mice. Lpl(m-/m-);Lep(ob/ob) mice also showed slower weight gain than Lep(ob/ob )mice, which was primarily due to reduced food intake. In conclusion, we discovered that the loss of myeloid Lpl led to extensive fibrosis of perigonadal WAT and hyper-triglyceridemia. In addition to illustrating an important role of macrophage LPL in regulation of circulating triglyceride levels, these data show that macrophage LPL protects against fibrosis in obese adipose tissues.
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