Reduced Growth and Inflammation in Lrp5^-/- Mice Adipose Tissue

Obesity is a major cause of chronic disease morbidity-mortality. Understanding the mechanisms triggering its promotion will allow the development of effective treatments. Cardiovascular diseases are associated with high-fat diet ingestion; however, how adiposity is distributed in relation to fat intake is not known. The lipoprotein receptor LRP5 participates in lipid handling in several cells. Whether LRP5 and its effector canonical WNT signalling pathway are involved in high-fat diet-induced adipose tissue distribution remains unknown. We fed Wt and Lrp5^-/- mice with a high cholesterol diet and analysed adipose and inflammatory markers. More fat deposition in Wt mice than in Lrp5^-/- mice is observed upon high-fat diet intake. Lipoprotein receptor expression is increased in mice visceral and subcutaneous adipose tissues of hypercholesterolemic mice. Gene expression markers of adiposity and inflammation show that LRP5 deficiency reduces adipocyte growth and differentiation while decreasing macrophage infiltration. LRP5 and LRP1 gene expression are also increased in human adipose tissues of obese patients, further suggesting that lipoprotein receptors participate in adipose tissue growth. In conclusion, LRP5 induces adipocyte proliferation and insulin sensitivity and, simultaneously, enhances macrophage's infiltrating capacity, triggering the inflammatory process associated with proliferating adipose tissues. This study shows that therapies can arise from research on canonical WNT signalling in adipose tissues to prevent obesity.