Why the study?
The role of macrophage-derived lipoprotein lipase in adipose tissue remodeling and lipoprotein metabolism during obesity was largely unknown.
Does loss of myeloid lipoprotein lipase exacerbate adipose tissue fibrosis and hyperlipidemia in leptin-deficient obese mice?
Does loss of myeloid lipoprotein lipase exacerbate adipose tissue fibrosis and hyperlipidemia in leptin-deficient obese mice?
Macrophage-derived lipoprotein lipase protects against adipose tissue fibrosis and regulates circulating triglyceride levels in obesity.
Myeloid LPL loss may worsen adipose fibrosis and hyperlipidemia in obese mice; leaves open any human therapeutic role.
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 perigonadal 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 α-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 hypertriglyceridemia. 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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Takahashi et al. (2022) studied this question.
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